Abstract
The aim of this study was to evaluate the visual attention of children with migraine and compare it with a control group. Thirty migrainous children and 30 controls without headache were subjected to a visual attention assessment with Trail Making Tests (TMT) A/B, Letter Cancellation Test, and the Brazilian computerized test Visual Attention Test, third edition. The migraine group was evaluated after 2 days without headache. The migraine group had an inferior performance compared with the control group on TMT A (P = 0.03) and B (P = 0.001), and more errors on tasks 1 (P = 0.032) and 2 (P = 0.015) of the Visual Attention Test, presenting difficulty with selective and alternate attention. Attention is a neurological function that depends on structures such as the brainstem, cerebral cortex and the limbic system and on neurotransmitters such as dopamine and noradrenaline. The neurochemical aspects involved in the physiopathology of migraine and attention mechanisms probably predispose these children to visual attention deficits.
Introduction
Migraine in childhood has prevalence rates ranging from 7.5% to 9.7% (1, 2), and despite being so usual and causing a great impact in children's lives (3), it still remains underdiagnosed and not appropriately treated (4).
Studies about cognitive dysfunction in paediatric migraine are scarce and display variable results (5–7), perhaps because they did not use control groups without migraine (7) or because they chose broad neuropsychological battery tests, lacking focus on a specific cognitive function (6, 7).
Riva et al. (7) reported worst visuomotor processing speed when compared children with migraine with (n = 17) and without (n = 31) aura, in both groups. D'Andrea et al. (5) found impairment in both short-term and long-term memory in the migraine group of a comparative study involving 20 children with migraine and 20 control children without migraine. However, Haverkamp et al (6) did not find any cognitive disturbances in migraineurs when compared with their siblings free of migraine.
In the adult population, Calandre et al. (8) found deficits in memory, attention, and information speed in migraineurs when compared with controls. Le Pira et al. (9) compared 30 individuals with migraine with controls and showed that immediate and delayed memory were impaired in subjects with migraine. Mulder et al. (10) found that migraineurs with aura performed worse on a measure of sustained attention than migraineurs without aura and controls. However, Leijdekkers et al. (11) and Pearson et al. (12) found no significant differences between migraine and control groups.
In the present study, we evaluated visual attention in children with migraine, comparing it with control children without headache.
Subject and methods
Sixty children participated in the study.
Migraine group: 30 patients, newly admitted to the out-patient childhood headache service at the Division of Investigation and Treatment of Headaches (DITH) of the Federal University of Sao Paulo; all diagnosed with migraine with (n = 5) or without aura (n = 25), according to the International Headache Society criteria (International Classification of Headache Diseases, 2nd edn, 2004) (13), 15 boys, aged 8–12 years (mean 10.8 ± 1.5 years), with an average of 5.8 ± 3.2 crises per month, lasting as long as 24 h and confirmed by a 30-day filled headache diary, without previous or current use of migraine prophylaxis.
Control group: 30 children without headache, 16 boys, similar age range (mean 9.9 ± 1.3 years), selected among two public schools in the city of Sao Paulo.
All children were submitted to medical and psychological evaluations. They were also evaluated using the Weschler Intelligence Scale for Children, third editon (14), applied by a DITH psychologist, and were included in the study if they had no other systemic illness, neurological abnormalities, intelligence quotient < 80, psychiatric disturbances, learning disabilities and history of epilepsy, head trauma or use of medications with action in the central nervous system, including drugs for migraine prophylaxis.
Informed consent was obtained from parents or tutors and the study was approved by our Local Research Ethics Committee.
All children were subjected to the following tests:
Trail Making Tests (TMT) A and B (for the paediatric age group). These tests explore visual attention, mental flexibility, visual scanning and psychomotor velocity; part B evaluates mainly alternate attention (15). In part A the subject being tested must connect numbers scattered on a paper sheet in an ascending sequence from 1 to 15; in part B the subject must likewise connect in an ascending sequence eight numbers and eight letters alternating between them. Both tasks should be executed in the shortest possible time and with no mistakes, execution in seconds being the main variable analysed in these tests (16).
Letter-Cancelling Test: a test for assessment of selective and sustained attention, in which the subject has to mark all the letters A randomly arranged together with other letters on a paper sheet, in the short possible period of time and with the minimum possible mistakes (17). The analysed variables were the time of execution in seconds and the number of omission errors (letters A not marked); Test of Visual Attention, third edition: this is a computerized test, standardized for the Brazilian population, which consists of three tasks: task 1 used for assessment of selective attention, task 2 for assessment of alternate attention and task 3 for sustained attention (18). In all of them, the subject tested uses a joystick and the main variables analysed are reaction time (which is the time in ms required to push the joystick button in face of the selected stimuli), number of omission errors (which is lack of response to the selected stimuli) and number of action errors (AE) (response to non-selected stimuli) (18).
All tests were administered in only one centre, in one session lasting from 40 to 60 min, by two DITH psychologists, between May 2006 and December 2007. All children with migraine had been free of pain and migrainous symptoms in the previous 2 days and at the time of the assessment.
Statistical analysis
For statistical analysis, Student's t-test and Mann–Whitney tests were used. The significance level was P ≤ 0.05.
Results
Results are reported in Table 1. Children with migraine performed significantly worse in TMT A (P = 0.03) and B (P = 0.001) and had a greater number of action errors in tasks 1 (P = 0.032) and 2 (P = 0.015) of the Visual Attention Test when compared with children without headache. The only variable in which we found no difference between groups was the reaction time of tasks in the Visual Attention Test. In all other variables the migraine group had an inferior performance when compared with the control group, but with a non-significant difference.
Results of visual attention assessment in migraine and control groups
∗ P < 0.05 and
∗∗ P < 0.001 in relation to control group.
Discussion
Children with migraine showed impairment in all variables in comparison with the control group, except on the reaction time in Visual Attention Test tasks. Although the performance in attention tasks was within normal range in both groups, the migraine group had difficulties in selective attention and mainly in alternate attention, which were assessed by TMT B and task 2 of Visual Attention Test. The great number of AEs also indicated high levels of impulsiveness in children with migraine, behaviour seen during the Wechsler Intelligence Scale for Children III and attention tests.
We did not find differences between migraineurs with and without aura, but this was probably due to the sample sizes (25 without aura and only five with aura) and resulting low statistical powers. Additionally, we did not observe a relationship between the duration of migraine and the attack frequency with attention impairment in the migraine group. In our sample we had children with a history of migraine ranging from 6 months to 5 years and with attack frequency ranging from one to 14 crises per month and, despite this, all migraineurs showed homogeneous performance in attention tasks. This was an interesting finding, and other studies (10, 19) have reported similar conclusions.
A possible explanation for our results could be found in the neurochemical aspects involved both in the physiopathology of migraine and in attentional mechanisms.
It is believed that noradrenaline and dopamine may have an important role in the physiopathology of migraine (20–22). Adequate levels of noradrenaline avoid hyperexcitability of the trigeminal system (23) and low levels predispose migraineurs to headache crises and to syncope (22). Also, secondary hypersensitivity of adrenergic receptors predispose these subjects to tachycardia and high pressure levels, more intense and long lasting when compared with patients without headache (22).
Dopamine acts on the trigeminal system by modulating neuronal excitability (24), playing an important role in the genesis of some prodromic symptoms, such as nausea and somnolence (25); also, patients with migraine show greater sensitivity to dopaminergic agonists (26).
Attention can be defined as the capacity to respond to significant stimuli to the detriment of others (27). It is a complex and important neurological function, highly dependent on a set of anatomical structures such as the brainstem, cerebral cortex and limbic system, as well as on a combination of neurotransmitters, chiefly noradrenaline and dopamine (28).
Noradrenaline maintains an adequate level of alertness, clearly revealing an important role in selective attention (the ability to focus on relevant stimuli, even when being distracted by other stimuli, and to select the information destined for conscious processing) and in alternate attention, and collaborates with maintenance of attention over time, acting both in the cortex as in subcortical structures, mainly through α2 receptors (28).
Dopamine displays high activity in the pre-frontal cortex and its connections with striatum and cingulate girus, modulating selective and sustained attention (28).
Disturbances of these neurotransmitters can cause attentional difficulties (29), as it can apparently play a part in the physiopathology of migraine, in mechanisms like pain generation as well as in other symptoms in the crisis and intercrisis periods (20–26).
In conclusion, it is supposed that variations in noradrenaline and dopamine levels in children with migraine predispose them to attentional deficits. Hence, in the cephaliatric anamnesis in childhood, an attentional questionnaire should be routinely performed.
It is very important that the evaluation of children with migraine be realized by a multidisciplinary team including, when necessary, neuropsychological assessment, in order to detect early cognitive dysfunctions. This kind of approach will lead to better planning of all the possible therapeutic strategies.