Sustained recovery of progressive multifocal leukoencephalopathy after treatment with IL-2

Abstract

A significant increase in hyperphosphorylated tau proteins (P-tau) in CSF has been shown in Alzheimer disease (AD), suggesting potential utility as biologic markers of AD. 1 Different subtypes of P-tau proteins perform differently in the discrimination of primary dementia disorders from AD. 2 Recently, we have shown that tau phosphorylated at threonine 231 (P-tau 231P ) correlates with cognitive decline in subjects with mild cognitive impairment (MCI), 3 a group at risk for AD. 4 Here, we examined in an exploratory study whether different P-tau epitopes differ in their accuracy to predict cognitive deterioration within subjects with MCI. Therefore, previously published results on P-tau 231P are again presented briefly for comparison. Moreover, we wished to know whether a combination of different P-tau epitopes is superior to a single P-tau marker for the prediction of cognitive decline.Three P-tau subtypes were measured at baseline in 59 patients with MCI. 4 Clinical follow-up was performed in all patients (mean interval 12.27 months, range 6 to 42 months). The mean (SD) age of the MCI patients (28 female) was 72.56 (7.6) years with a mean Mini-Mental State Examination (MMSE) score of 28.0 (1.9). There were 23 healthy control subjects (HC; 14 female; age 60.0 Ϯ 10.1 years; MMSE 29.2 Ϯ 0.7 points). Study subjects were recruited at two centers (Department of Psychiatry, Ludwig Maximilian University, Munich, Germany, and Department of Clinical Neuroscience, Göteborg, Sweden). P-Tau epitopes including P-tau 231P , tau protein phosphorylated at threonine 181 (P-tau 181P ), and serine 199 (P-tau 199P ) were measured using ELISAs. 2,3 Prediction of annual rate of cognitive decline (measured by MMSE change) was tested for each P-tau epitope in a separate multiple linear regression model. With use of a forward selection method, for each model, age, gender, MMSE at baseline, duration of interval, center, treatment with cognitive enhancers, and the baseline level of the respective P-tau epitope were entered as variables. A variable was entered into the model if the p value

Progressive multifocal leukoencephalopathy: current treatment options and future perspectives

“…Stimulates growth of T-cell lymphocytes and provides other biochemical signaling to the immune system None Benefit claimed in individual case reports [Przepiorka et al 1997;Re et al 1999;Buckanovich et al 2002;Kunschner and Scott, 2005] IL-7 (CYT107)…”

Case Files of the New York City Poison Control Center: Paradichlorobenzene-Induced Leukoencephalopathy

“…Treatment of chronic anemia with erythropoietin, particularly in end-stage renal failure patients, can cause hypertension associated with posterior leukoencephalopathy [50]. Although some agents like interleukin 2, interferon, and prednisone have been reported to precipitate reversible posterior leukoencephalopathy, they have also been used to treat progressive multifocal leukoencephalopathy with variable success [51,52].…”

Central Nervous System Infections in Cancer Patients and Hematopoietic Stem Cell Transplant Recipients

“…Previous investigations established a 0.07 % incidence of PML in those with hematologic malignancies [249], although the disease frequency may be increasing as a result of the introduction of potent immunomodulatory therapies into clinical practice [245,250]. There are multiple descriptions of PML complicating the course of leukemia [243,[251][252][253][254][255][256][257], lymphoma [243,254,[258][259][260][261], myelodysplastic syndrome [262], mycosis fungoides [263], multiple myeloma [264], polycythemia vera [265], and Waldenstrom's macroglobulinemia [266]; following fludarabine therapy [253,254]; and affecting those undergoing HSCT [267][268][269][270][271][272][273][274][275][276][277]. There are increasing reports of PML in patients receiving immunomodulatory therapies, especially rituximab [259-261, 275, 278-283], mycophenolate mofetil [284], and alemtuzumab [285].…”

“…Therapies with interleukin-2 [250,262,268,271,275], intravenous immunoglobulin [250], cidofovir [250,275,289,290], topotecan [291], and nucleoside analogs such as cytarabine [248,250,275] have been attempted, but successful treatment is limited to anecdote, and no clear benefit is demonstrated in any clinical trials with these agents. In stem cell transplant recipients, withdrawal of GVHD prophylaxis and donor lymphocyte infusions has been tried as therapy for PML [243].…”