Brainstem auditory-evoked responses among children afflicted by severely hypoxic CHD.

MAIN AIM: To electrophysiologically determine the impact of moderate to severe chronic hypoxia (H) resulting from a wide array of CHD (HCHD) conditions on the integrity of brainstem function. MATERIALS AND METHODS: Applying brainstem auditory-evoked response methodology, 30 chronically afflicted HCHD patients, who already had undergone heart surgery, were compared to 28 healthy control children (1-15 yo) matched by age, gender and socioeconomic condition. Blood oxygen saturation was clinically determined and again immediately before brainstem auditory-evoked response testing. RESULTS: Among HCHD children, auditory wave latencies (I, III and V) were significantly longer (medians: I, 2.02 ms; III, 4.12 ms, and; V, 6.30 ms) compared to control (medians: I, 1.67ms; III, 3.72 ms, and; V, 5.65 ms), as well as interpeak intervals (HCHD medians: I-V, 4.25 ms, and; III-V, 2.25ms; control medians: I-V, 3.90 ms and, III-V, 1.80 ms) without significant differences in wave amplitudes between groups. A statistically significant and inverse correlation between average blood oxygen saturation of each group (control, 94%; HCHD, 78%) and their respective wave latencies and interpeak intervals was found. CONCLUSIONS: As determined by brainstem auditory-evoked responses, young HCHD patients manifestly show severely altered neuronal conductivity in the auditory pathway strongly correlated with their hypoxic condition. These observations are strongly supported by different brainstem neurological and image studies showing that alterations, either in microstructure or function, result from the condition of chronic hypoxia in CHD. The non-altered wave amplitudes are indicative of relatively well-preserved neuronal relay nuclei.

Iron therapy substantially restores qEEG maturational lag among iron-deficient anemic infants.

OBJECTIVE: To use quantitative electroencephalography (qEEG) to assess the impact of iron-deficiency anemia on central nervous system maturation in the first year of life. METHOD: Twenty-five infants (3-12 months old) presenting ferropenic anemia (IDA) and 25 healthy controls (CTL1), matched by age/gender with the former, were studied in two stages. Electroencephalogram during spontaneous sleep was recorded from all participants; the fast Fourier transform was calculated to obtain absolute power (AP) and relative power (RP) qEEG measures. In the first stage, a qEEG comparison between CTL1 and IDA was performed. Second stage consisted in comparing qEEG of the IDA infants before and after supplementation with iron (IDA-IS group), and comparing qEEG of the IDA-IS group with another control age-matched group (CTL2). Non-parametric multivariate permutation tests (NPT) were applied to assess differences between CTL1 and IDA groups, as well as IDA vs. IDA-IS, and IDA-IS vs. CTL2. RESULTS: More power in slow frequency bands and less power in fast frequency bands in 64% of IDA babies were observed. NPT evinced higher alpha AP and RP (P < 0.001), less theta AP, and less delta and theta RP in CTL1 than in IDA. After iron-restoration therapy, alpha AP and RP increased while theta AP and theta and delta RP decreased, reaching almost normal values. DISCUSSION: This work reveals CNS developmental delay through the study of qEEG (less rapid and more slow frequencies) which recovered significantly with iron supplementation. It is concluded that IDA constitutes a high risk factor for a lag of CNS maturation.

Molecular mechanisms of cognitive impairment in iron deficiency: alterations in brain-derived neurotrophic factor and insulin-like growth factor expression and function in the central nervous system.

OBJECTIVE: The present review examines the relationship between iron deficiency and central nervous system (CNS) development and cognitive impairment, focusing on the cellular and molecular mechanisms related to the expression and function of growth factors, particularly the insulin-like growth factors I and II (IGF-I/II) and brain-derived neurotrophic factor (BDNF), in the CNS. METHODS: Nutritional deficiencies are important determinants in human cognitive impairment. Among these, iron deficiency has the highest prevalence worldwide. Although this ailment is known to induce psychomotor deficits during development, the precise molecular and cellular mechanisms underlying these alterations have not been properly elucidated. This review summarizes the available information on the effect of iron deficiency on the expression and function of growth factors in the CNS, with an emphasis on IGF-I/II and BDNF. RESULTS AND DISCUSSION: Recent studies have shown that specific growth factors, such as IGF-I/II and BDNF, have an essential role in cognition, particularly in processes involving learning and memory, by the activation of intracellular-signaling pathways involved in cell proliferation, differentiation, and survival. It is known that nutritional deficiencies promote reductions in systemic and CNS concentrations of growth factors, and that altered expression of these molecules and their receptors in the CNS leads to psychomotor and developmental deficits. Iron deficiency may induce these deficits by decreasing the expression and function of IGF-I/II and BDNF in specific areas of the brain.

[Electroencephalographic and neurodevelopmental disorders in toddlers with severe congenital heart diseases. Preliminary study]. / Alteraciones electroencefalográficas y del neurodesarrollo en niños portadores de cardiopatías congénitas severas. Estudio preliminar.

UNLABELLED: Within the field of pediatric heart disease, congenital cardiopathology is the most important issue due to the fact that in these patients a delay of neurodevelopment is the most frequent morbidity. The major aim of this work was to determine the impact of severe congenital cardiopathology (SCC) on the central nervous system (CNS) through the study of the electroencephalogram (EEG) and the assessment of neurodevelopment. POPULATION AND METHODS: Children under 3 years old, 41 of them presenting SCC and 15 healthy controls (C) were studied. Conventional EEG recording and assessment of neurodevelopment were performed. RESULTS: In twenty children presenting SCC (48.8%) the EEG was found abnormal (paroxysmal of spikes and sharp waves). Forty of them (97.6%) presented neurodevelopmental alterations, including hypotonia and a delay in gross motor skills. When comparing EEG between SCC and C children, odds ratio was 13.33 (1.602-111) and comparing neurodevelopment delay, it was 35 (3.769-235). Both were statistically significant (p ≤ 0.00039 and p ≤ 0.00038, respectively). CONCLUSIONS: A high percentage of children suffering from SCC exhibited EEG patterns with abnormal epileptic-like activity although without clinical manifestation of seizures. These children also showed delay features in different areas of neurodevelopmental. The assessment of new born carrying some type of severe cardiopathology indicated that they were under high risk of suffering from CNS altered development.

Neurobehavioral assessment of children presenting diverse congenital cardiopathologies.

Brain maturation in 1-36 month old children suffering from congenital cardiopathologies was assessed after a study of psychomotor development. The Rogers' test (Rogers et al., Developmental programming for infants and young children. Volume 2. Early intervention developmental profile, Revised edition, ESL/ELT Michigan, Ann Arbor, 1981) was applied to 65 children, of whom 21 presented with simple cardiopathologies (CpS) and 22 with complex cardiopathologies (CpC). All children were matched by age, sex and socioeconomic status to 22 healthy children in a control group (C). Mean differences between the three groups were established by applying the Kruskal-Wallis test, and mean differences between the C and CpS/CpC groups were determined using the Mann-Whitney test. The proportion of cases evaluated as "low" in each group was calculated by applying the Rogers' test, and a test of proportion differences was applied between the C and CpS/CpC groups. CpS children performed similarly to the C, whereas CpC children scored significantly lower than C children on all variables. It is highly likely that the suboptimal psychomotor performance observed in CpC children was due to compromised hemodynamics and related to subclinical immaturity of cerebral development.

Working memory impairment and recovery in iron deficient children.

OBJECTIVE: Iron is an important oligoelement participating in multiple metabolic processes, including the synthesis of catecholamines, and its deficiency (ID) throughout development is particularly insidious on brain maturation and the emergence of cognitive functions during school age. A working memory (WM) study in 8-10-year-old ID children is presented. It is hypothesized that an impairment in WM exists in ID school-age children and a substantial restoration of this mental ability should occur after iron supplementation. METHODS: Event-related potentials (ERPs) were recorded during the completion of a Sternberg-type task in control, ID and ID-iron supplemented children. RESULTS: ID children showed less correct answers and diminished ERP amplitude in frontal, central, parietal and temporal regions compared to control children. After iron supplementation and normalizing bodily iron stores, behavioral and ERP differences disappeared between ID and control children. CONCLUSIONS: Considering that WM is fundamentally related to attention ability, the results presented here confirm and reinforce previous observations: ID severely diminishes attention [Otero GA, Pliego-Rivero FB, Contreras G, Ricardo J, Fernandez T. Iron supplementation brings up a lacking P300 in iron deficient children. Clin Neurophysiol 2004;115:2259-66] and WM while iron supplementation substantially restores the cognitive capabilities tested. SIGNIFICANCE: This is one of very few reports using ERP showing a diminished WM capability in ID school-age children.

Delayed CNS maturation in iron-deficient anaemic infants.

Direct evidence of CNS developmental alterations in iron-deficient anaemic (IDA) infants was obtained. Twenty 3-15-month-old IDA and 20 non-IDA infants (age and gender matched), healthy in every other respect, were studied. Complete blood and iron kinetics tests determined an IDA status. Psychomotor development was assessed through the test of Rogers and co-workers [Rogers SJ, Donovan CM, D'Eugenio D, Brown SL, Whiteside E, Moersch MS, Schafer DS. (eds) Developmental Programming for Infants and Young Children, Vol 2. University of Michigan Press, 1981] and under the 10-20 International System qEEG was performed (sleep/stage II). A Pearson's correlation test was applied between haematological, psychomotor and broad band EEG variables, and through ANOVA psychomotor and AP means were compared. IDA infants showed lower scores in cognition, fine motor and social/emotional areas, higher delta/theta and lower alpha power. Most correlations between haematological/psychological variables were positive. Delta/theta correlations were negative with self-care/gross and motor items while alpha/beta AP showed positive correlations with psychomotor and haematological variables. A clear association was found between EEG alterations and a low haematological/iron profile leading to a delayed psychomotor development.

Relationship of working memory and EEG to academic performance: a study among high school students.

Some biological and behavioral elements which could explain differences between high and low academic attainment (HA/LA) students were identified. The qEEG of subjects under the 10-20 derivation system was recorded at rest and while completing a 3-back working memory (WM) task. While completing the task LA students showed more theta and total absolute potency at rest, and HA individuals showed more energy in delta and theta frequencies in frontal regions; LA students made a higher number of mistakes while executing the WM task with no differences in reaction time between groups. We conclude that a diminished WM capacity is present in LA students.