Effect of high dose cytosine arabinoside on quantitative EEG in patients with acute myeloid leukemia

Abstract

Background EEG activity is considered an index of functional state of brain. Chemotherapy (CT), used for non-central nervous system (CNS) cancer, can cross the blood brain barrier and contribute to changes in the functional state of brain that can alter background EEG activity. Quantitative EEG (qEEG) is superior to conventional EEG in the detection of subtle alterations of EEG background activity and for this reason, the use of qEEG might assist the clinician in evaluating the possible effect of CT on the CNS. The nucleoside analog cytosine arabinoside (Ara-C) is one of the milestone chemotherapeutic agents used for treatment of acute myeloid leukemia (AML). Our observational study evaluates the possible effect of Ara-C on the qEEG of patients with AML, without CNS involvement. We conducted an observational study on newly diagnosed AML patients without CNS involvement, undergoing treatment with Ara-C to analyze the possible effect of Ara-C high doses on EEG background activity using qEEG analyses. A total of nine AML patients, 5 with Ara-C i.v. high dose (C3 g/m 2 die), 4 with standard dose (100 mg/m 2 die) underwent qEEG (at rest, during hyperpnoea, mental arithmetic task and blocking reaction). We compared the EEG background activity of the two groups at baseline and after 6 months. Statistical analysis showed no significant differences between the two groups in mean relative power for all frequency bands, at rest and during hyperpnoea, mental arithmetic task and blocking reaction. Our data indicate that high dose Ara-C i.v. did not induce significant changes on EEG background activity in our patients. Future research in this area could include prospective studies that would combine qEEG and neuropsychological testing to assess the impact of CT on brain functions.

The usefulness of sLORETA in evaluating the effect of high-dose ARA-C on brain connectivity in patients with acute myeloid leukemia: an exploratory study

“…Nevertheless, sLORETA is a novel approach for the evaluation of chemotherapy-related effects on functional connectivity and electrical brain activity, which represents a step forward with respect to other techniques described in the literature. Indeed, in Maschio et al (2016), qEEG was used for evaluating Ara-C-induced toxicity, but this approach failed to reveal changes in EEG background activity caused by high-dose Ara-C administration. Thus, sLORETA analysis, providing an accurate measure of electrophysiological connectivity, seems to be more effective in detecting changes in functional connectivity and electrical brain activity.…”

“…Despite these benefits, qEEG is also associated with "the problem of volume conduction and active reference electrodes in the assessment of functional connectivity", which can result in spurious correlations between time series recorded from neighboring electrodes (Stam et al, 2007). With regard to Ara-C, the effect of this drug on EEG background activity was recently investigated by Maschio et al (2016) using qEEG. The past decade has seen the development of more suitable methods for localizing electrical activity and exploring functional brain connectivity, such as "standardized LORETA" (sLORETA), a low-resolution EEG tomography method for evaluating brain electromagnetic activity (Pascual-Marqui et al, 1994).…”