The endogenous potentials analyzed in current study are the result of changes in the electrical voltage associated with information processing. They do not depend directly on the type of stimulus but on thinking processes and are classified as long-latency potentials constituting an electrophysiological indicator of cognitive processes . The P300 potential is determined by the positive wave with the highest amplitude recorded in the central-parietal midline leads in response to the processing of the auditory or visual stimulus. Stimulation with two distinct acoustic stimuli (oddball paradigm) is commonly used. The P300 wave arises after 300–800 ms. This wave occurs when the stimulus recognition is associated with a high level of subjective uncertainty and is a measure of the degree of attention devoted to a particular cognitive task. It is assumed that it is generated in the hippocampus and in the temporal and parietal lobes of the cerebral cortex .
Among the greatest advantages of neurophysiological techniques are their high sensitivity, non-invasiveness and the ability to repeat them at relatively low costs. They are an objective although non-specific neurological diagnostic tool. Endogenous potentials are widely used in clinical practice, in particular in the diagnosis of oligosymptomatic disease processes, mainly dementia syndromes . Their serial execution also allows to track the dynamics of the disease process and monitor the treatment, therefore they are helpful in determining the prognosis.
However, the usefulness of event-related potentials in the diagnosis and monitoring of adverse effects of childhood ALL treatment has not been sufficiently understood yet. As already mentioned, event-related potentials reflect the synchronized post-synaptic potentials generated by the depolarization of neurons, primarily the large pyramidal cells of the cerebral cortex. Its latency is a measure of the time needed for the cognitive processes preceding the cognitive assessment of the task situation, while the wave amplitude defines the involvement of cognitive structures. The changes observed by us indicate slower and more effortful target detection. Prolonged latency and a reduction in the amplitude of the P300 potential have already been shown in ALL survivors. However, all previous studies have been conducted on small groups of patients. P300 latency has been found to peak later and to have a smaller amplitude in childhood cancer survivors [13, 18]. However, a study by Lahteenmaki et al.  was performed on a heterogeneous group of only 19 cancer survivors, in which there were 11 patients with ALL. In turn, Uberall et al. included only 13 long-time ALL survivors in their study. Our results are also consistent with the results by Sato et al.  who showed a significant increase in P300 latency in 33 patients treated with chemotherapy and radiotherapy compared to patients treated with chemotherapy alone and to the control group. Moore et al. also made similar observations on an equally large group of childhood cancer survivors . Järvelä et al. demonstrated the usefulness of P300 potentials in monitoring of central nervous system toxicity of ALL therapy in 27 patients. They showed a relationship between progressive deterioration of mental performance and prolongation of the peak latency as well as poorer enhancement of P300 amplitude after treatment . The previous observations presented above have also been confirmed by recently published preliminary results by Brace et al. . Decreased amplitude of particular P300 components were observed in the analyzed small group of 8 ALL survivors treated exclusively with chemotherapy protocols.
Our study may also have potential therapeutic implications in the future. N-methyl-D-aspartate (NMDA) channels have a central role in the generation of event-related potentials . Differences in particular parameters of P300 potentials between ALL survivors and controls are consistent with altered neurotransmission through NMDA receptors . Recent preclinical study has revealed that memantine, non-competitive NMDA receptor antagonist, reduces the incidence of cognitive deficits in rats treated with intrathecal methotrexate . Memantine has also shown promising effects in randomized trial among adults treated with cranial radiation for brain tumors . Potentially, a group of patients with subtle neurocognitive dysfunction identified on the basis of screening with P300 event-related potentials can therefore experience the benefits of prophylactic use of NMDA antagonists. Such behavior may protect this selected group of patients from the development of symptomatic cognitive impairment. However, large randomized trials using NMDA antagonists in patients with childhood ALL are necessary to confirm this hypothesis.
Our study has several limitations. First, our study compared different protocols previously used in clinical practice. However, it was our deliberate intention. Thanks to this it is possible to study the impact of radiotherapy withdrawn from many protocols currently used in ALL on P300 potentials. Second, neuroimaging and neuropsychological correlations with neurophysiological results were not performed. However, the purpose of our study was only to evaluate the value of cognitive disorders screening. The performed neurophysiological studies informed about maintaining the functional integrity of the nervous system. However, none of the patients exceeded the 5% margin of uncounted discriminating stimuli which indicates the correct concentration of attention. It should also be emphasized that all patients carried out their school duty in an undisturbed manner or they worked and were fully independent after completing their education. Third, genetic methods, which are increasingly used in the diagnosis of cognitive disorders in the pediatric population, have not been used [25, 26].