The first descriptions of the neurological disease associated with HTLV-1 infections were based on the motor function assessed by mobility and strength disability [1, 2]. The HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP) is a chronic, slow-progressing neurological inflammatory disease that affects approximately 4% of the infected individuals [3, 4]. However, the prevalence of neurological disorders that do not meet the criteria for definite HAM/TSP, such as urinary disorders, sexual dysfunction and skin lesions, can occur in around 30% of those individuals classified as HTLV-1-asymptomatic carriers [4–6]. In fact, non-medullary symptoms have been neglected in the HTLV-1 infection [7].
Recent evidences have showed that HTLV-1 is related to a complex of neurological manifestations that are not limited to the clinical spectrum of HAM/TSP, affecting all the segments of the central nervous system to a greater or lesser extent [3, 8–18]. In this context, cognitive impairment has been reported as one of the manifestations of the HTLV-1 infection [11, 13, 19–24]. On the other hand, HAM/TSP remains as the most important neurological disease associated with HTLV-1 [25, 26]. Therefore, cognitive impairment can be underdiagnosed and may go unnoticed in those individuals who do not spontaneously report the decline in cognitive functions [27].
Memory difficulties are present in HTLV-1 infection at different stages of the neurological disease and the worsening in the performance of daily tasks, together with electrophysiological changes, can be an early sign of cognitive impairment when the individual is in the stage of asymptomatic infection [11, 12, 20, 21, 28, 29].
The working memory reflects the capacity of retaining crucial information for immediate processing and use. It is important for everyday tasks, for everyday reasoning and decision-making processes [30]. The working memory difficulties have been reported as a sign of cognitive impairment associated to HTLV-1 infection at different stages of this neurological disease [12, 20, 21, 28, 29]. Recently, it has been suggested, based on a complete neuropsychological exam battery, that memory dysfunction in the HTLV-1-neurological spectrum may occur between the asymptomatic and the HAM/TSP stages [21] and it could be related to a neurological impairment caused by subcortical and cortical white matter lesions [28, 31]. The worsening in memory functioning, along with electrophysiological alterations, may be an early sign of cognitive impairment in HTLV-1 asymptomatic infection [11]. Therefore, a challenge in the diagnosis and clinical management of this population is to differentiate the true asymptomatic infection from the “non-HAM/TSP” neurological signs since the clinical phenotype of HTLV-1 neurological manifestations appears to be wide and underdiagnosed.
Event-related potentials (ERPs) are the brain’s response to specific sensory or cognitive events. The auditory P300 ERP is commonly elicited through an oddball task and consists of neural activity originating from presumably the prefrontal cortex, the temporoparietal junction, the primary auditory cortex and possibly more sources [32]. The P300 ERP has been associated with the stimulus driven frontal attention mechanisms during task processing and working memory [33, 34]. P300 has a relatively large size wave in comparison to the other components of the ERPs, which makes it easier to detect, so that it has been used to test early cognitive impairment in the clinical practice [35–38].
One study evaluated patients with HAM/TSP and controls using different evoked potentials, including P300, and found that P300 latency was significantly increased in the HAM/TSP group when compared to the health controls. Delayed P300 response in the HAM/TSP group was associated with higher prevalence of cognitive impairment that was detected by cognitive screening and image exams [19].
Another electrophysiological test that has been used to improve the diagnostic accuracy in HTLV-1 neurological manifestation is the vestibular evoked myogenic potential (VEMP) [10, 15–17, 39]. VEMP was able to assess the extent of neurological impairment in HTLV-1 infection and to detect mesencephalic alteration in 70.1% of the HAM/TSP patients and in 11.5% of the asymptomatic carriers [10]. In fact, recent publications have called attention to global cognitive impairment and the executive dysfunction as long-term clinical manifestations linked to a persistent inflammatory activity in the central nervous system that usually occurs in this disease [13].
The memory complaint, especially for everyday tasks and situations, is frequent in individuals with some degree of cognitive impairment. Although some studies have refuted the association between self-reported measures and the diagnosis of cognitive impairment [40, 41], the presence of subjective memory complaints has been systematically used as a starting point for a more detailed investigation of possible cognitive changes [42–45]. The self-report of a subjective cognitive decline has been accepted to have a predictive value for mild cognitive impairment and it has been seen in the earliest stages of Alzheimer's disease [43–46]. The visual scales, either presenting numbers, figures, or both, have been used to test the self-perception of cognitive impairment [46, 47]. These scales are easy to apply during a medical consultation and could be included in the HTLV-1 neurological exam battery.
The objective of the present study was to evaluate the applicability of a self-perceived memory score and P300 for the early detection of cognitive impairment in HTLV-1-infected people going from the stage of asymptomatic carrier to the definite HAM/TSP.