|Year : 2020 | Volume
| Issue : 4 | Page : 199-202
A rare case of progressive multifocal leukoencephalopathy – As a presenting manifestation of AIDS
S Sumangala, Mohd Zeeshan Ali, Mushtaq Saudagar
Department of General Medicine, M R Medical College, Gulbarga, Karnataka, India
|Date of Submission||11-Aug-2019|
|Date of Acceptance||15-Dec-2019|
|Date of Web Publication||23-Oct-2020|
Dr. S Sumangala
Department of General Medicine, M R Medical College, Gulbarga, Karnataka
Source of Support: None, Conflict of Interest: None
Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating central nervous system (CNS) infection disease that exclusively affects immunocompromised individuals. John Cunningham virus, the etiologic agent for PML, is ubiquitous in the general population but rarely causes disease in immunocompetent hosts. Here, we present a 35-year-old male with left hemiparesis and loss of vision, diagnosed as PML as the first AIDS-defining event, with previously undiagnosed human immunodeficiency virus (HIV) infection. PML is an underinvestigated CNS infection seen in HIV patients usually with advanced disease. We present an unusual case report, where PML occurred as the first AIDS-defining event in a patient with previously undiagnosed HIV infection. This case is presented to enlighten the physicians regarding the clinical entity of PML to be suspected in HIV-infected patients who present with focal neurologic deficits even in undiagnosed infection.
Keywords: Acquired immune deficiency syndrome, John Cunningham virus, progressive multifocal leukoencephalopathy
|How to cite this article:|
Sumangala S, Ali MZ, Saudagar M. A rare case of progressive multifocal leukoencephalopathy – As a presenting manifestation of AIDS. APIK J Int Med 2020;8:199-202
|How to cite this URL:|
Sumangala S, Ali MZ, Saudagar M. A rare case of progressive multifocal leukoencephalopathy – As a presenting manifestation of AIDS. APIK J Int Med [serial online] 2020 [cited 2020 Nov 30];8:199-202. Available from: https://www.ajim.in/text.asp?2020/8/4/199/298935
| Introduction|| |
Human immunodeficiency virus (HIV) infection is a global menace with over 5 million people living with HIV/AIDS in India. HIV is known to be a neurotropic virus, and central nervous system (CNS) involvement is seen as presenting complaints in 10% of cases, with a spectrum of neurological manifestations. The prominent demyelinating CNS lesions reported in HIV are acute disseminated encephalomyelitis and multiple scleroses such as demyelination and progressive multifocal leukoencephalopathy (PML). PML is a rare and usually fatal viral disease occurring almost exclusively in people with severe immune deficiency, leading to severe disability or death. PML is the result of the reactivation of latent John Cunningham virus (JCV) infection in the setting of cellular immunodeficiencies. Here, we present a 35-year-old male with left hemiparesis and loss of vision, diagnosed PML as the first AIDS-defining event, with previously undiagnosed HIV infection.
| Case Report|| |
A 35-year-old male, laborer by occupation, right-handed male presented to casualty with 6-week history of progressive neurological symptoms manifesting as a progressive painless diminution of vision in both eyes, followed by weakness of the left upper limb and lower limb for 1 month. Weakness has initially started in the left upper limb in the distal part which progressed to involve the proximal limb which gradually progressed to involve the left lower limb over the next 20 days. He was associated with a history of deviation of angle of mouth to the right side, and slurring of speech was present.
There was a history of high-risk sexual behavior. There was no history of seizures, fever, vomiting, headache, head injury, jaundice, and ear discharge. There was no history of any prior medical illness. He was a smoker and a social drinker. He was married and had two children. On examination, the patient was afebrile. Vitals were stable. He was cooperative and oriented to time, place, and person. The examination of visual acuity revealed that the patient was able to perceive only the light stimulus. Both direct and consensual light reflexes were intact. The fundus examination was normal, and there were no features suggestive of cytomegalovirus retinitis. Extraocular movements were free and full in all directions. There was left upper motor neuron facial nerve palsy. Speech appeared to be slurred, but the comprehension was intact. There was motor weakness of the left upper limb and lower limb with the power of 0/5 in both. The tone was increased in all the four limbs with the presence of the left ankle clonus. The plantar reflex was extensor on the left side. The patient was responding to painful stimulus. Cerebellar signs could not be assessed. There were no meningeal signs present. Skull and spine examination was normal. Rest of the systemic examination was normal.
The complete blood picture showed lymphopenia (10%). Liver enzymes were deranged. Renal functions and urine examination were normal. Tridot card test (solid-phase immunoassay) revealed the presence of antibodies to HIV 1 virus. It was confirmed by the Western blot assay. The patient was nonreactive to HIV 2, hepatitis B virus surface antigen, and hepatitis C virus. CD4 T-cell count was 93 cells/mm3, magnetic resonance imaging (MRI) brain plain and contrast, as shown in the figure [Figure 1], showed diffuse hyperintense areas involving bilateral parietooccipital, subcortical deep white matter, dorsomedial thalamus, distal body and splenium of the corpus callosum. These areas did not reveal the true restriction on apparent diffusion coefficient and diffusion-weighted imaging sequences, and there was no mass effect. The postcontrast study revealed minimal gyral enhancement in bilateral parietooccipital lobes. These features revealed the postinfectious or postinflammatory tumefactive demyelination changes, which were consistent with PML like changes in neuroradiology.
|Figure 1: Magnetic resonance imaging brain imaging - clockwise from the top left: T1-weighted; T2-weighted; diffusion-weighted imaging; fluid-attenuated inversion recovery; apparent diffusion coefficient; T1 weighted postcontrast; showing diffuse hyperintense areas involving bilateral parieto occipital, sub cortical deep white matter, dorsomedial thalamus, distal body and splenium of corpus callosum. These areas did not reveal true restriction on the apparent diffusion coefficient and diffusion-weighted imaging sequences and there was no mass effect. Postcontrast - minimal gyral enhancement in bilateral parieto occipital lobes|
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Analysis of cerebrospinal fluid (CSF) was done which revealed five cells (100% lymphocytes), CSF protein was 129 mg/dl, and sugar was 76 mg/dl (less than two-third of plasma sugar). The microscopic examination did not reveal the presence of any organism. CSF culture did not reveal the growth of any organism. CSF PCR for TB bacilli and Herpes simplex virus were negative. JCV PCR revealed the presence of ≥50 lakh copies/ml. On the basis of the patient's clinical, laboratory investigations, radiological picture and after ruling out other possibilities, we formulated a diagnosis of PML. The patient was transferred to the regional ART center for the initiation of highly active antiretroviral therapy (HAART). The patient's condition worsened progressively and died after 20 days.
| Discussion|| |
PML is a demyelinating disease of CNS. It is most commonly caused by JCV, a human polyomavirus (DNA virus) belonging to Papovaviridae group and rarely by the BK virus . PML was first diagnosed by a German neuropathologist, Hallervorden. The JCV was isolated in 1971 by Padgett and Walker, which is a DNA-containing polyomavirus. The JCV has been shown to persist in the kidneys and is shed in the urine. More than 80% of the human adult population is seropositive for JCV-specific immunoglobulin G antibodies. Despite this high prevalence of infection, JCV induced disease is rare, occurring almost exclusively in immunosuppressed individuals. Since the onset of the AIDS epidemic in 1981, the incidence of PML has increased significantly, and now HIV-associated cases account for up to 85% of all cases of PML. PML has been estimated to affect 4% of patients with HIV infection. The non-AIDS population affected by PML is middle aged and usually harbors either an underlying lymphoproliferative, myeloproliferative, granulomatous disorder or receiving immunosuppressive therapy.
The pathogenesis of PML is divided into three phases. The primary infection is usually asymptomatic, with approximately 85% of the adult population showing antibodies against the JCV, and thereafter, the virus remains as a persistent latent infection in the urinary tract, bone marrow, and spleen. The final phase is related to the reactivation and dissemination of the virus with an almost certain hematogenous spread to the CNS. PML is the only known clinical manifestation of JCV infection.
The neurologic signs and symptoms of PML result from the viral destruction of the myelin-producing oligodendrocytes in the CNS. The main pathologic features are atypical astrocytes with enlarged multilobulated nuclei and intranuclear inclusion in oligodendrocytes, which are JCV particles on in situ hybridization. The clinical features are progressive in focal neurological dysfunction. Commonly aphasia/dysarthria, monoparesis, hemiparesis, ataxia, cortical blindness, or visual field defects are reported. Mental status changes such as confusion, dementia, and even coma are seen. Seizures are infrequent (<10%). There are no clinical features of raised intracranial pressure or of systemic infection.
The CSF biochemistry and cytology are normal. In CSF, detection of JCV by the PCR is diagnostic [Table 1]. The sensitivity is 70%, and specificity is 90%–100%. In negative PCR for JCV repeat CSF examination or brain biopsy is advocated, which is confirmatory for diagnosis. Recent improvements in newer imaging techniques like MR spectroscopy are replacing the older invasive methods for diagnosing PML.
|Table 1: Diagnostic criteria for progressive multifocal leukoencephalopathy|
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MRI offers superior sensitivity in the detection and characterization of the lesions though the diagnosis may be suspected by computed tomography scan. On T2-weighted images, the lesions appear hyperintense and typically involve the paraventricular and subcortical white matter having scalloped lateral margin when they involve the subcortical white matter predominantly in the parietooccipital lobes. Lesions are more conspicuously visualized in the fluid-attenuated inversion recovery sequences, appearing hyperintense against a background of suppressed CSF signal intensity. Mass effect is infrequently described and usually minimal and correlation with shorter survival when seen on the initial studies. The pattern may be unilateral, but more often bilateral and asymmetrical with the involvement of posterior fossa as seen in our case. PML may also involve the basal ganglia and deep white nuclei, as there are white matter fibers in these regions. The lesions typically do not enhance and do not have mass effect; however, there have been some reports of peripheral mild or diffuse enhancement. In those cases, enhancement suggests a good immune response, and hence, improves the prognosis. There have been reports with lesions, having cystic components suggesting tumors or abscess. On MR spectroscopy, there is reduced N -acetyl aspartate (NAA) with a significant decreased NAA/creatine ratio with increased choline and lactate peak.
A combination of typical clinical features and typical imaging findings supports a “presumptive diagnosis” of PML. For a “definitive diagnosis,” along with clinical and imaging findings, there should be evidence of JCV in CSF or typical histopathological changes with demonstration of JCV DNA in the infected cells.
Currently, there is no specific antiviral agent for the JCV infection, and the existing treatment goal in PML is to restore the host adaptive immune response (e.g., antiretroviral therapy if HIV infection). Although the results were unsatisfactory, a number of specific drugs against the JCV (such as cidofovir, topotecan, cytarabine, mefloquine, and mirtazapine) have been investigated. Mirtazapine has been implicated in preventing the progression of PML in some case reports. HAART at present is the most effective treatment for PML. It is postulated that HAART reduces the viral load and thus improving the immune function.
In our case, associating the positive CSF JCV PCR results in the highly suggestive clinical and imaging findings, it was possible to establish the diagnosis of PML. The cause of viral reactivation in our case was secondary to immunosuppression due to HIV.
| Conclusion|| |
PML is a rare, devastating demyelinating disease of the CNS caused by the JCV that occurs in patients with compromised immune systems. PML is most commonly seen in patients with a known diagnosis of AIDS, but it can be the presenting AIDS-defining illness. To conclude, it is imperative for the general physicians to be aware that HIV can present as subacute or acute neurologic deficits as the first AIDS-defining illness in a relatively immunocompetent patient.
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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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