Final Diagnosis -- Cerebral Schistosomiasis Caused by Schistosoma Mansoni


DIAGNOSIS

Atypical gliosis with reactive changes, no evidence of mantle cell lymphoma. The overall features are suggestive of progressive multifocal leukoencephalopathy (PML).

An in-situ hybridization study performed at a referring medical center (Mayo Clinic) for JC virus was positive (Fig. 5).

DISCUSSION

The John Cunningham (JC) virus is a polyoma virus that causes Progressive Multifocal Leukoencephalopathy (PML), a demyelinating disorder of the CNS. The JC virus infects glial cells including both astrocytes and oligodendrocytes, and some neurons (1,2). Replication within oligodendrocytes causes cell lysis and myelin breakdown (1). Histologically, variable lymphocytic inflammation and reactive gliosis with bizarre astrocytes are often seen in addition to demyelination with microglia/macrophages and residual oligodendrocytes containing abnormal nuclear inclusions (1). Clinically, PML presents as deficits corresponding to the location of the lesions, which tend to be localized in the subcortical areas of the cerebrum (1,2). In this case, the cerebellar lesion caused coordination problems, dizziness, and gait abnormalities.

It has been theorized that most people are infected in childhood by an archetype JC virus strain that is unable to invade glial cells. The archetype virus establishes latency in various body sites where it must undergo mutations of the non-coding control region in order to become neurotropic and replicate inside glial cells (4). However, only those who become immunosuppressed have the potential to progress to PML (4).

PML occurrence initially increased during the HIV era, when 5% of HIV patients developed PML (2). Recently, monoclonal antibodies such as natalizumab, efalizumab, and rituximab have been shown to increase susceptibility to development of PML. Rituximab targets CD20+ B lymphocytes causing cell death and depletion, and it has been used effectively with chemotherapy regimens for treatment of non-Hodgkin lymphoma (NHL) as well as some autoimmune diseases (3). The mechanism involved in rituximab causing PML is still an unresolved issue (4).

With limited drug options, treatment for PML has been focused on recovery of the immune system (1). Rapid increase in the cellular response, usually after starting cART therapy in HIV+ patients or discontinuation of immunosuppression in HIV- patients, can cause Immune Reconstitution Inflammatory Syndrome (IRIS) characterized by severe inflammation and worsening of symptoms not explained by the original PML disease (1,3). MRI shows contrast enhancement, mass effect, or swelling, which are absent in PML without IRIS (2). Optimal care of PML patients with immune reconstitution must be closely monitored for possible IRIS complications (1).

The current patient's mantle cell lymphoma remains in remission and she has not shown clinical progression of her PML with conservative supportive therapy.

REFERENCES

  1. Clifford DB. (2015) Progressive multifocal leukoencephalopathy therapy. J Neurovirol 6:632-6
  2. Gheuens S, Wuthrich C, Koralnik IJ. (2013) Progressive multifocal leukoencephalopathy: Why gray and white matter. Ann Rev Pathol Mech Dis 8:189-215.
  3. Jelcic I, Jelcic I, Faigle W, Sospedra M, Martin R. (2015) Immunology of progressive multifocal leukoencephalopathy. J Neurovirol 6:614-622.
  4. Wollebo HS, White MK, Gordon J, Berger JR, Khalili K. (2015) Persistence and pathogenesis of the neurotropic polyomavirus JC. Ann Neurol 77(4):560-70.

Contributed by Robert Conway, BA, Vesna Kaluza, MD, Kenneth Schwartz, MD, Howard T. Chang, MD, PhD




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