Successful Resolution of Progressive Multifocal Leukoencephalopathy after Combination Therapy with Cidofovir and Cytosine Arabinoside

Martínez, A Chocarro; López, A González; Garcia, Isidra

doi:10.1086/313574

Cited by 9 publications

(1 citation statement)

References 4 publications

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“…The use of anti-HIV-1 drugs failed to produce neurological improvement in patients with PML, but did prolong their survival. Cidofovir and cytosine arabinoside, which have both anti-herpes and anti-polyomavirus activity, were helpful in one case [43]. Valacyclovir has been tested in MS, but with little success so far [44,45].…”

Section: Conclusion Significance and Guidelines For Treatmentmentioning

confidence: 99%

HHV-6, Not JC Virus, Causes Demyelination in PML Connections Between HHV-6, HIV-1 and JC Virus in Multiple Sclerosis, Neuro-AIDS and PML A Commentary and Review Offering Guidelines for Treatment

Blumberg¹

2016

J Neurol Disord

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In recent years, two outstandingly effective drugs for the treatment of multiple sclerosis (MS) have appeared on the market: Tysabri® (Biogen Idec/Elan, 2008) and Gilenya® (Novartis, 2010). Tysabri (Natalizumab) is a humanized monoclonal antibody that binds to the cellular adhesion molecule alpha-4 integrin, which is used by lymphocytes to cross vascular walls and penetrate the blood-brain barrier. Tysabri thus reduces the flux of infected or autoimmune lymphocytes into the CNS. Gilenya (Fingolimod) is an immunomodulatory drug that acts on the sphingosine-1-phosphate receptor to sequester lymphocytes in peripheral lymph nodes, thus also indirectly reducing the flux of infected or autoimmune lymphocytes into the CNS. Both drugs have great clinical promise for treating MS, but both have revealed a critical shortcoming: their use increases the risk of Progressive Multifocal Leucoencephalopathy (PML), a demyelinating disease worse than MS and quickly fatal if not controlled. PML arises in individuals whose immune function is compromised, such as patients undergoing chemotherapy for various kinds of cancer. During the early years of the AIDS epidemic (approximately from 1986-1999), the incidence of PML rose in parallel with increasing numbers of immunocompromised AIDS patients, then fell after effective combined aggressive retrovirus treatment (cART) for HIV-1/AIDS became widely available (after 2000-2001). Unfortunately, the incidence of PML is now rising again in conjunction with the increased use of Tysabri and Gilenya in treating MS. It is therefore important to identify effective treatment modalities for PML.

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Section: Conclusion Significance and Guidelines For Treatmentmentioning

confidence: 99%

HHV-6, Not JC Virus, Causes Demyelination in PML Connections Between HHV-6, HIV-1 and JC Virus in Multiple Sclerosis, Neuro-AIDS and PML A Commentary and Review Offering Guidelines for Treatment

Blumberg¹

2016

J Neurol Disord

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Focal Neurological Disease in Patients with Acquired Immunodeficiency Syndrome

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2002

Clinical Infectious Diseases

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Focal neurological disease in patients with acquired immunodeficiency syndrome may be caused by various opportunistic pathogens and malignancies, including Toxoplasma gondii, progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV), and Epstein-Barr virus-related primary central nervous system (CNS) lymphoma. Diagnosis may be difficult, because the findings of lumbar puncture, computed tomography (CT), and magnetic resonance imaging are relatively nonspecific. Newer techniques have led to improved diagnostic accuracy of these conditions. Polymerase chain reaction (PCR) of cerebrospinal fluid specimens is useful for diagnosis of PML, CNS lymphoma, and CMV encephalitis. Recent studies have indicated the diagnostic utility of new neuroimaging techniques, such as single-photon emission CT and positron emission tomography. The combination of PCR and neuroimaging techniques may obviate the need for brain biopsy in selected cases. However, stereotactic brain biopsy, which is associated with relatively low morbidity rates, remains the reference standard for diagnosis. Highly active antiretroviral therapy has improved the prognosis of several focal CNS processes, most notably toxoplasmosis, PML, and CMV encephalitis.

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Clinical Course and Prognostic Factors of Progressive Multifocal Leukoencephalopathy in Patients Treated with Highly Active Antiretroviral Therapy

et al. 2003

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We analyzed survival rates, neurologic function, and prognostic factors for 118 consecutive patients with acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) in 11 hospitals throughout Spain. Seventy-five patients (63.6%) remained alive for a median of 114 weeks (2.2 years) after diagnosis of PML. Neurologic function of the survivors was categorized as cure or improvement in 33, stabilization or worsening in 40, and unknown in 2. The baseline CD4+ cell count was the only variable found with prognostic significance. The odds ratio of death was 2.71 (95% confidence interval, 1.19-6.15) for patients with CD4+ cell counts of <100 cells/microL, compared with patients who had CD4+ cell counts of > or =100 cells/microL. One-third of patients with PML died despite receipt of HAART; neurologic function improved in approximately one-half of the survivors. A CD4+ cell count of <100 cells/microL was associated with higher mortality.

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Successful Resolution of Progressive Multifocal Leukoencephalopathy after Combination Therapy with Cidofovir and Cytosine Arabinoside

Cited by 9 publications

References 4 publications

HHV-6, Not JC Virus, Causes Demyelination in PML Connections Between HHV-6, HIV-1 and JC Virus in Multiple Sclerosis, Neuro-AIDS and PML A Commentary and Review Offering Guidelines for Treatment

HHV-6, Not JC Virus, Causes Demyelination in PML Connections Between HHV-6, HIV-1 and JC Virus in Multiple Sclerosis, Neuro-AIDS and PML A Commentary and Review Offering Guidelines for Treatment

Focal Neurological Disease in Patients with Acquired Immunodeficiency Syndrome

Clinical Course and Prognostic Factors of Progressive Multifocal Leukoencephalopathy in Patients Treated with Highly Active Antiretroviral Therapy

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