Drugs Smarter Than the Bugs: Mirtazapine and Mefloquine for Non‐Aids‐Related Progressive Multifocal Leukoencephalopathy

1Marshfield Clinic, Marshfield, WI
2Marshfield Clinic, Marshfield, WI

Meeting: Hospital Medicine 2013, May 16-19, National Harbor, Md.

Abstract number: 412

Case Presentation:

A 77‐year‐old man with chronic lymphocytic leukemia (CLL) and hypogammaglobulinemia was hospitalized for generalized seizures. Three weeks prior to admission he was found to have progressive psychomotor slowing. Head CT revealed an area of low attenuation involving the frontal lobe with effacement of the cortical sulci and vasogenic edema. MRI demonstrated an abnormal signal in the left frontal lesion with edema and feathered enhancement pattern. He was started on Fosphenytoin for seizures and dexamethasone for vasogenic edema. Histopathologic evaluation of tissue biopsy from left frontal lobe lesion showed prominent reactive gliosis, frequent bizarre astrocytes and florid perivascular lymphocytic infiltrates. The lymphocytes were mostly small sized along with large macrophages in the adjacent brain tissue. Immunohistochemical stains confirmed this is to be exclusively a T‐cell lymphocytic infiltrate around vessels and within the parenchyma. Very few B.‐cells were present. John Cunningham (JC) virus in situ hybridization study was positive. HIV was nonreactive. The patient was treated with mirtazapine 30 mg daily and mefloquine 250 mg daily for 3 days followed by 250 mg once weekly. Follow‐up 13 months later showed some improvement in cognitive function. MRI of the head showed the diffusion abnormality, scant posterior contrast enhancement, and mass effect were significantly resolved.

Discussion:

Progressive multifocal leukoencephalopathy (PML) invades oligodendrocytes in the central nervous system white matter causing demyelination and neurologic deficits. PML affects patients with lymphoreticular malignancy (e.g., CLL or non‐Hodgkin's lymphoma), AIDS, organ transplantation, etc. To date, there are no satisfactory treatments for PML. Although spontaneous partial recovery and prolonged survival have been reported, the disease is progressive with 80% mortality within 9 months. Reduction or withdrawal of immunosuppressants in patients with non‐AIDS PML and the use of HAART in AIDS‐related PML is the only known interventions that may allow immune reconstitution and control of pathological viral activity. The 5‐HT2A serotonin receptor has been found to act as a receptor for JCV in glial cells. The use of serotonin receptor blockers that are selective for the 5‐HT2A receptor, such as mirtazapine and risperidone, is physiologically plausible. The antimalarial drug mefloquine has recently been recognized to have anti‐JCV activity at nontoxic concentrations within vitro culture and passes the blood–brain barrier to achieve concentrations in the brain above the level inhibiting JCV replications in vitro.

Conclusions:

The recent trial of mefloquine in 21 patients with AIDS and 3 without AIDS failed to show a reduction in JC viral DNA levels in the CSF. The positive clinical response seen in our patient after the initiation of combination therapy (Mirtazapine and Mefloquine) suggest that further studies in the form of randomized controlled trials in non AIDS PML using this combination therapy is warranted.

To cite this abstract:

Epperla N, Yale S. Drugs Smarter Than the Bugs: Mirtazapine and Mefloquine for Non‐Aids‐Related Progressive Multifocal Leukoencephalopathy. Abstract published at Hospital Medicine 2013, May 16-19, National Harbor, Md. Abstract 412. Journal of Hospital Medicine. 2013; 8 (suppl 2). https://www.shmabstracts.com/abstract/drugs-smarter-than-the-bugs-mirtazapine-and-mefloquine-for-nonaidsrelated-progressive-multifocal-leukoencephalopathy/. Accessed May 26, 2019.

« Back to Hospital Medicine 2013, May 16-19, National Harbor, Md.