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.

EEG effective connectivity during the first year of life mirrors brain synaptogenesis, myelination, and early right hemisphere predominance.

INTRODUCTION: The maturation of electroencephalogram (EEG) effective connectivity in healthy infants during the first year of life is described. METHODS: Participants: A cross-sectional sample of 125 healthy at-term infants, from 0 to 12 months of age, underwent EEG in a state of quiet sleep. PROCEDURES: The EEG primary currents at the source were described with the sLoreta method. An unmixing algorithm was applied to reduce the leakage, and the isolated effective coherence, a direct and directed measurement of information flow, was calculated. RESULTS AND DISCUSSION: Initially, the highest indices of connectivity are at the subcortical nuclei, continuing to the parietal lobe, predominantly the right hemisphere, then expanding to temporal, occipital, and finally the frontal areas, which is consistent with the myelination process. Age-related connectivity changes were mostly long-range and bilateral. Connections increased with age, mainly in the right hemisphere, while they mainly decreased in the left hemisphere. Increased connectivity from 20 to 30 Hz, mostly at the right hemisphere. These findings were consistent with right hemisphere predominance during the first three years of life. Theta and alpha connections showed the greatest changes with age. Strong connectivity was found between the parietal, temporal, and occipital regions to the frontal lobes, responsible for executive functions and consistent with behavioral development during the first year. The thalamus exchanges information bidirectionally with all cortical regions and frequency bands. CONCLUSIONS: The maturation of EEG connectivity during the first year in healthy infants is very consistent with synaptogenesis, reductions in synaptogenesis, myelination, and functional and behavioral development.

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.

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.

Iron supplementation brings up a lacking P300 in iron deficient children.

OBJECTIVE: A decrease in iron concentration is accompanied by alterations in catecholaminergic and GABAergic neurotransmission systems, important in learning, memory and attention. It was hypothesized that iron deficient children would present attention deficits. A visual-event related potentials (ERPs) study is presented using an oddball paradigm in order to determine the P300 in ID children. METHODS: After medical examination, blood was obtained from 201 children for a complete hematological study. Two groups were selected, iron deficient (ID) (serum iron <60 microg/dl) and control (C) (serum iron >60 microg/dl). In both groups ERPs were recorded while executing a continuous performance task (oddball paradigm). Afterwards iron levels were restored in ID children by iron supplementation (ID-IS group) and all tests reapplied. RESULTS: ID children almost lacked a P300 in central and parietal regions. After iron supplementation, P300 clearly became evident although its Pz amplitude remained smaller compared to C children. CONCLUSIONS: A clear and strong correlation was found between ID and attention alterations in children. Iron supplementation nearly brings the P300 to normal levels although it is not known if the P300 difference in Pz is due to other nutritional/environmental deficits or to developmental psychomotor impairments in ID children. SIGNIFICANCE: It has been long known that iron deficient children have cognitive impairments but there is an insufficient number of electrophysiological works allowing to identify the source of this problem. In this work an attention deficit is demonstrated in ID children through a severely reduced P300, which recovers substantially after iron supplementation.