Effective use of JC virus PCR for diagnosis of progressive multifocal leukoencephalopathy

Yihong Wang1, James E Kirby1, Qinfang Qian1

  • 1Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

Insights

JC virus (JCV) PCR testing on cerebrospinal fluid (CSF) is most effective in diagnosing progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected patients with low CD4 counts and severely immunocompromised individuals.

Area of Science:

  • Neurology
  • Virology
  • Immunology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic demyelinating disease.
  • JC virus (JCV) is the causative agent of PML.
  • Diagnosis of PML often relies on clinical presentation, imaging, and JCV detection.

Purpose of the Study:

  • To evaluate the diagnostic utility of JCV PCR in cerebrospinal fluid (CSF) for suspected PML.
  • To identify patient populations most likely to benefit from JCV PCR testing.

Main Methods:

  • Retrospective review of 168 patients with suspected PML between 1996 and 2006.
  • Analysis of JCV PCR results from CSF samples.
  • Correlation with patient immune status (HIV infection, CD4 cell counts) and radiographic findings.

Main Results:

  • JCV PCR was positive in HIV-infected patients with low CD4 counts and severely immunocompromised patients with PML-consistent lesions.
  • One HIV patient with a very low CD4 count tested positive for JCV PCR despite a normal MRI.
  • Testing yielded positive results primarily in high-risk patient groups.

Conclusions:

  • JCV PCR testing on CSF is a valuable diagnostic tool for PML.
  • Targeting JCV PCR testing to HIV-infected patients with low CD4 counts and severely immunocompromised individuals improves diagnostic yield.
  • JCV PCR can detect infection even in the absence of typical radiographic findings.

Related Concept Videos

Arboviral Encephalitis01:25

Arboviral Encephalitis

Arboviral encephalitis refers to brain inflammation caused by arthropod-borne viruses, particularly those transmitted through mosquito vectors. Among these, West Nile virus (WNV), a member of the Flaviviridae family, is a significant public health concern. WNV is an enveloped, positive-sense, single-stranded RNA virus. Human infection typically begins when an infected mosquito introduces the virus into the dermis during feeding. The primary transmission cycle involves birds as amplifying hosts...
Encephalitis l: Introduction01:19

Encephalitis l: Introduction

Encephalitis is inflammation of the brain parenchyma, most often due to infections or autoimmune processes. It presents with neuropsychiatric features such as fever, altered mental status, behavioral changes, cognitive dysfunction, seizures, focal deficits, and sometimes autonomic instability. In some cases, the meninges are also involved, resulting in meningoencephalitis.Infectious CausesInfectious encephalitis is most commonly viral but can also result from bacterial, fungal, or parasitic...
Cytomegalovirus Disease01:27

Cytomegalovirus Disease

Cytomegalovirus (CMV) disease is caused by human cytomegalovirus, a double-stranded DNA virus of the Herpesviridae family. While primary CMV infection is often asymptomatic in immunocompetent individuals, the virus can cause severe disease in neonates and immunocompromised patients. CMV is the most common cause of congenital viral infection in the United States, and a major pathogen in solid organ and hematopoietic stem cell transplant recipients.CMV is transmitted via bodily fluids, sexual...
Cryptococcal Meningitis01:27

Cryptococcal Meningitis

Cryptococcal meningitis is a life-threatening opportunistic infection predominantly associated with HIV/AIDS, accounting for over 100,000 deaths annually worldwide. However, it also affects individuals with other forms of immunosuppression, including those undergoing immunosuppressive therapy, organ transplant recipients, patients with innate immunodeficiencies, and individuals with hematological disorders. The infection is caused mainly by Cryptococcus neoformans and Cryptococcus gattii,...
Encephalitis ll: Pathophysiology01:26

Encephalitis ll: Pathophysiology

Encephalitis is inflammation of the brain parenchyma caused by direct viral invasion or immune-mediated mechanisms triggered by infections or tumors. Both processes lead to neuronal injury, disrupted neurotransmission, and diverse neurological symptoms, often with overlapping clinical and pathological features.Autoimmune EncephalitisIn autoimmune encephalitis, antibodies target neuronal antigens on cell surfaces, synapses, or within neurons. A key example is anti-NMDAR encephalitis, which can...
Enzyme-Linked Immunosorbent Assay01:33

Enzyme-Linked Immunosorbent Assay

In 1971, Peter Perlman and Eva Engvall developed an Enzyme-linked immunosorbent assay (ELISA or EIA). ELISA differs from western blot in that the assays are conducted in microtiter plates or in vivo rather than on an absorbent membrane.
There are many different types of ELISAs, but they all involve an antibody molecule whose constant region binds an enzyme, leaving the variable region free to bind its specific antigen.  Enzyme-substrate reaction allows the antigen to be visualized or quantified.