Correspondence

Remission of Progressive Multifocal Leukoencephalopathy Following Splenectomy and Antiretroviral Therapy in a Patient with HIV Infection

N Engl J Med 1997; 336:661-662February 27, 1997

Article

To the Editor:

Progressive multifocal leukoencephalopathy caused by JC papovavirus infection of glial cells is an increasingly frequent complication of human immunodeficiency virus (HIV) type 1 infection. To date, there is no treatment available for progressive multifocal leukoencephalopathy, and it usually results in death within three to six months of diagnosis.1 We report on a 30-year-old man with hemophilia and AIDS (CD4 count, 64 cells per cubic millimeter) who was being treated with d4T and Septra and who came to our clinic with a two-week history of headache, diplopia, and left-arm ataxia. The patient had a normal mental status (HIV dementia scale, 14 of 16), left-sided gaze-evoked nystagmus and right beating nystagmus in the primary gaze position, and a marked intention tremor with slowed rapid alternating movements on the left side. A magnetic resonance imaging (MRI) scan revealed a nonenhancing lesion in the left cerebellar hemisphere without mass effect (Figure 1AFigure 1T₂-Weighted MRI Scan Showing a Cerebellar Lesion at Presentation (Panel A) and Seven Months after the Diagnosis of Progressive Multifocal Leukoencephalopathy (Panel B).). Brain biopsy of the lesion showed oligodendrocytes with enlarged nuclei (Figure 2Figure 2Section of the Cerebellar-Biopsy Specimen Showing an Oligodendroglial Nuclear Inclusion (Arrow) and a Normal Nucleus (Arrowhead) (Hematoxylin and Eosin, ×225).), infiltrating macrophages (Figure 2), and lymphocytes on histologic analysis; JC virus inclusions were identified by electron microscopy. Because of previous reports suggesting that splenectomy increased CD4 levels in HIV infection2,3 and reduced viral load in simian immunodeficiency virus infection,4 the patient underwent a complete splenectomy three weeks after presentation. The patient's initial HIV viral load was 9.6×10⁵ copies per milliliter. After splenectomy, the patient was also treated with saquinavir, zidovudine, and lamivudine. Three weeks after the splenectomy, the HIV viral load decreased to 1.1×10⁵ copies per milliliter. The patient's tremor and ataxia in the left arm improved markedly without evidence of nystagmus. The patient continued to do well, and at the seven-month follow-up, his HIV viral load was 6×10³ copies per milliliter. A repeated MRI scan revealed only scarring from the biopsy and marked reduction in the left cerebellar lesion (Figure 1B).

Although spontaneous remissions may rarely occur in patients with progressive multifocal leukoencephalopathy, this patient, who had poor prognostic markers including a CD4 cell count of <200 cells per cubic millimeter, absence of contrast enhancement on MRI scan, and an infratentorial lesion,5 made a remarkable recovery. The improvement in this patient, concurrent with a drop in viral load, indicates that combination therapy of multiple antiretroviral agents with splenectomy may have been beneficial. We suggest that multiple antiretroviral agents, splenectomy, or both may contribute to the decreased viral load of HIV-1 and JC virus, which are both lymphocyte-tropic.1 Hence, aggressive combination treatment of patients with progressive multifocal leukoencephalopathy may be warranted.

Christopher Power, M.D.
Avi Nath, M.D.
Fred Y. Aoki, M.D.
Marc Del Bigio, M.D., Ph.D.
University of Manitoba, Winnipeg, MB R3E 0W3, Canada

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