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Correspondence

Contrast-enhancing progressive multifocal leukoencephalopathy as an immune reconstitution event in AIDS patients

Collazos, Julio; Mayo, Jose; Martínez, Eduardo; Blanco, Maria-Soledad

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Abstract

Although it has been reported in previous studies [1,2], contrast enhancement is not a characteristic feature of progressive multifocal leukoencephalopathy (PML), and the finding of enhancing lesions suggests that other conditions are involved. We would like to report four patients with such atypical features.

Patient 1

A 40-year-old man developed psychomotor disturbances 2 months after the onset of highly active antiretroviral therapy (HAART). His CD4 cell count increased from 166 to 300/μl, and viral load fell from 113679 to 460 RNA copies/ml. Magnetic resonance imaging (MRI) showed subcortical white matter lesions in both cerebellar hemispheres, with slight peripheral enhancement after gadolinium contrast. HAART was continued with improvement.

Patient 2

A 37-year-old man complained of weakness in his right arm 5 weeks after the initiation of HAART. His CD4 cell count increased from 26 to 332/μl, and viral load decreased from 220000 to 1200 copies/ml. MRI revealed several lesions in the left frontal lobe, which showed peripheral enhancement. HAART was continued with improvement.

Patient 3

A 30-year-old woman complained of unstable gait. Her CD4 cell count was 126/μl, and MRI revealed non-enhancing lesions in the cerebellum and pons. She was treated with zidovudine and didanosine. Seventeen months later her clinical condition had improved slightly, the CD4 cell count was 95/μl, and viral load was 11000 copies/ml. Treatment was changed to lamivudine, stavudine and saquinavir. Two months later, the patient felt improved, CD4 cell count was 151/μl, and viral load was undetectable. However, MRI revealed an increase in the number of lesions with respect to the previous study, which showed slight enhancement after gadolinium. Treatment was continued with improvement.

Patient 4

A 27-year-old man developed coordination disturbances in his right arm and leg. MRI showed non-enhancing lesions in the left hemisphere and the cerebellar peduncles. One month later symptoms had worsened. Another MRI revealed an increase in the size and number of the lesions with intense peripheral enhancement. By then his CD4 cell count had increased from 42 to 153/μl and viral load had decreased from 224000 to 1200 copies/ml. Treatment was continued with improvement of symptoms, but with initial progression of the lesions.

These four observations, as well as isolated cases previously reported [3,4], strongly suggest that contrast-enhancing PML may be observed, especially in patients who conserve a certain degree of immunocompetence or in whom immune reconstitution is achieved by HAART. This immunocompetence would result in a greater inflammatory response against JC virus [5], which may be responsible for the contrast enhancement observed in the MRI studies. In fact, mononuclear inflammation was observed in the area of enhancement but not in the non-enhancing areas in two reports [3,4].

Like these four patients, other patients with inflammatory PML had relatively high CD4 cell counts at the time of diagnosis [3,4]. Of note, patients 3 and 4 of the present series had non-enhancing lesions when severely immunosuppressed, and developed enhancement with gadolinium only when their CD4 cell counts had increased. In addition, two out of three patients who developed PML as a result of the initiation of HAART developed enhancing PML, whereas the patient who did not have enhancement only showed a modest increase from 22 to 57 CD4 cells/μl at the time of evaluation [6].

Table 1 shows the follow-up findings of the four patients. All patients in this series showed a clear clinical and MRI improvement with HAART that extended for 7-36 months of follow-up after the onset of symptoms. Interestingly, in all four patients the lesions had turned from enhancing to non-enhancing in the follow-up MRI studies performed 3 to 6 months later. In the above-mentioned report [6], the only patient who did not have enhancing lesions also improved from a clinical and MRI point of view, but he did not develop enhancing lesions despite a further increase in his CD4 cell count up to 114/μl. These observations suggest that inflammatory PML is particularly characteristic of patients who experienced substantial immunological reconstitution during the first weeks of therapy. Remarkably, inflammatory PML have been associated with a more favourable prognosis in both HIV-negative and HIV-positive patients, even in the absence of treatment [7], which supports the role that immune status plays on the development of this condition.

Table 1
Table 1:
Follow-up CD4 cell counts, viral load, symptoms and magnetic resonance imaging studies referred to the time of the enhancing magnetic resonance imaging

To our knowledge, this is the first series documenting the appearance of inflammatory PML associated with immune recovery. We believe that contrast-enhancing PML are expected to increase as AIDS patients are surviving longer, and there is effective therapy for severely immunosuppressed patients. Inflammatory PML should be suspected in patients with contrast-enhancing lesions on MRI, particularly in cases with relatively preserved immunity, and when the patient has experienced immune reconstitution after HAART.

References

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