Neurological bases of behavioral development in infancy.

This article presents selected psychological competences that emerge in children during the first 2 years, together with correlated structural, biochemical and physiological changes in the brain. Major behavioral events of the 1st year are the disappearance of the neonatal reflexes, the improvement of recognition and working memory and the appearance of the universal fears of strangers and of separation from the caretaker. These behaviors are correlated in time with changes in the brain that allow the increased ability of the cortex to inhibit brainstem reflexes, with processes in the prefrontal cortex and hippocampus that facilitate the formation, storage and retrieval of memories, and with strengthened connections between the cortex and limbic system.

Neurobiological bases of behavioral development in the second year.

We discuss selected psychological competences that develop and become noticeable between one and two years of age and are temporally correlated to structural, biochemical and physiological changes in the brain. The psychological competences are: Language development, a sense of "right" and "wrong", self-awareness, and the ability to make inferences. The accompanying changes in the brain involve the prefrontal cortex, language-related cortical areas, hippocampus, cerebellum, basal ganglia and an increase in the connectivity of the network.

Neurobiological bases of behavioral development in the first year.

This review summarizes the temporal relations between selected psychological milestones in the first year of the human infant and theoretically relevant developmental neurobiological changes in the brain, supplemented where appropriate, with evidence from the non-human primate. The disappearance of the palmar grasp reflex and the decrease in endogenous smiling and spontaneous crying, which occur at 2-3 months, are correlated to emergent cortical inhibition of brainstem circuits. In addition, the improved ability to recognize an event experienced in the immediate past (recognition memory) is related to growth of the hippocampus and adjacent structures at this age.

Structural and neurobehavioral delay in postnatal brain development of preterm infants.

Postnatal brain development of healthy prematurely born infants was assessed to study possible influence of premature birth and early extrauterine environment on structural, biochemical, and functional brain development. Myelination and differentiation of gray and white matter were studied by in vivo magnetic resonance (MR) imaging (MRI), changes in cerebral metabolism by 1HMR spectroscopy (MRS), and changes in early human neurobehavior by the assessment of preterm infant's behavior (APIB). The stage of intrauterine and extrauterine brain development in prematurely born infants at term was compared with the stage of mainly intrauterine brain development in a group of full-term infants.

The dynamics of brain concentrations of phenylalanine and its clinical significance in patients with phenylketonuria determined by in vivo 1H magnetic resonance spectroscopy.

Cerebral concentrations of phenylalanine (PHE) were measured by means of quantitative in vivo 1H MR spectroscopy in 8 adult patients treated early for phenylketonuria type I. A 1.5-Tesla routine magnetic resonance scanner, localization sequence with short echo time (20 ms), and a fully automated data processing scheme were used.

Identification and quantitation of phenylalanine in the brain of patients with phenylketonuria by means of localized in vivo 1H magnetic-resonance spectroscopy.

Localized proton MR spectroscopy was used to identify phenylalanine (PHE) and to quantitate its cerebral concentration in patients with type I phenylketonuria (PKU). Data acquisition was optimized for the detection of low-concentration metabolites, using a short TE (20 ms) double Hahn-echo localization sequence for large volumes within the head coil and for smaller volumes using a surface coil. Previously described methods to quantitate localized MR spectra were extended to cover the case of low-concentration metabolites, unevenly distributed in three brain compartments and measured in difference spectra only.

In vivo proton magnetic resonance spectroscopy in a case of Reye's syndrome.

A case of a 14-year-old boy with Reye's syndrome (RS) and complete neurologic recovery is presented. 1H magnetic resonance spectroscopy was performed on days 1 (admission to ICU), 8 and 62: During the acute phase of RS substantial cerebral metabolic imbalances were observed and their normalization monitored. The spectra from day 1 featured extremely high glutamine content (approximately 18 mmol/kg excess) and low concentrations of choline compounds pounds (approximately 1 mmol/kg deficit).

In vivo measurement of phenylalanine in human brain by proton nuclear magnetic resonance spectroscopy.

Disorders of the CNS are the major causes of morbidity and mortality observed in untreated subjects with phenylketonuria (PKU). A method to measure cerebral concentrations of phenylalanine (Phe) in vivo would greatly enhance the ability to investigate both the pathophysiology and the efficacy of therapy of this aminoacidopathy. Twelve image-guided localized proton nuclear magnetic resonance spectroscopic studies were performed in seven subjects with PKU using pulse sequences optimized to detect the aromatic protons of Phe.

Regional metabolic assessment of human brain during development by proton magnetic resonance spectroscopy in vivo and by high-performance liquid chromatography/gas chromatography in autopsy tissue.

To study the course of regional metabolite concentrations during early brain development, we measured in vivo metabolites [N-acetyl-aspartate (NAA), choline-containing compounds, and myoinositol (M-Ino)] in the precentral area of the cerebrum by short echo-time single volume proton magnetic resonance spectroscopy and compared in vivo established spectroscopic data with classic chromatographic data (HPLC) on age-corresponding autopsy tissue in different regions of the brain. In autopsy tissue, regional (frontal lobe, precentral area, basal ganglia, thalamus) and age-dependent differences of the concentration of creatine, NAA, and M-Ino were determined. In vivo measurement of NAA by proton magnetic resonance spectroscopy shows a significant increase of NAA by increasing postconceptional age.

Retarded development of neurons and oligodendroglia in rat forebrain produced by hyperphenylalaninemia results in permanent deficits in myelin despite long recovery periods.

The severe hypomyelination seen in the CNS of untreated phenylketonuria (PKU) patients has been suggested to be the result of a defect in the process of myelination itself. Using chronic hyperphenylalaninemia (HPA) in rats as a model of PKU we have previously shown, by immunohistochemistry, that axonal maturation as well as myelination was severely retarded. In the present study we have used image analysis techniques to quantitate changes in myelin basic protein (MBP) and 200-kDa neurofilament protein (NF-H) immunostaining in the corpus callosum and cerebral cortical grey matter of HPA rats.

Compound heterozygosity for metachromatic leukodystrophy and arylsulfatase A pseudodeficiency alleles is not associated with progressive neurological disease.

Several allelic mutations at the arylsulfatase A (ASA) locus cause substantial deficiencies of this lysosomal enzyme. Depending on the genetically determined degree of the deficiency, the clinical outcome may be very different--either metachromatic leukodystrophy (MLD), a lethal lysosomal storage disorder affecting the nervous system, or, more frequently, the so-called pseudodeficiency (PD), which has no apparent clinical consequence. Because of compound heterozygosity for MLD and PD, 1/1,000 individuals in the population have low residual enzyme activities, which are intermediate between those of MLD patients and those of PD homozygous normal individuals.

Short echo time proton MR spectroscopic imaging.

Proton spectroscopic imaging at short TEs (20-30 ms) in human brain requires volume preselection inside the brain to suppress overwhelming lipid and water signals from surrounding tissue. In this article we discuss limitations of conventional volume preselection using stimulated echoes that lead to spectral contamination from surrounding tissue. Improved volume preselection was obtained by adding a complete outer volume suppression (presaturation).

Hartnup syndrome, progressive encephalopathy and allo-albuminaemia. A clinico-pathological case study.

Clinical, biochemical, neuropathological and neurochemical findings in a case of Hartnup syndrome are reported. After initially normal development, the affected girl suffered progressive neuropsychiatric decline with statomotor and mental retardation and intractable seizures and died at the age of 2 years. Postmortem neuropathological and neurochemical investigations showed a combination of extensive neuronal degeneration and cerebral dysmyelination.

Disturbed myelinogenesis and recovery in hyperphenylalaninemia in rats: an immunohistochemical study.

Chronic hyperphenylalaninemia (HPA) in rats has been used as an experimental model of the human inborn error of metabolism phenylketonuria (PKU). Impaired brain development in PKU and HPA is reflected in reduced myelin formation. We have used immunohistochemistry, with antibodies to cell-specific antigenic markers, to investigate the cellular basis of the hypomyelination in the corpus callosum and cerebral cortex of rats made hyperphenylalaninemic from Postnatal Days 3-17.

Magnetic resonance in preterm and term newborns: 1H-spectroscopy in developing human brain.

Localized proton magnetic resonance spectra were recorded from human cerebellum in vivo with a 1.5-T magnet. The spectra from healthy adults and preterm and term babies showed resonances from N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds such as phosphocholine and glycerophosphocholine, taurine, and inositol.

Prenatal stroke suggested by intrauterine ultrasound and confirmed by magnetic resonance imaging.

Cerebral infarction is rare in premature newborns and is most commonly the result of arterial embolization from the placenta. A focal echodense area was identified on prenatal cranial ultrasonography (US) in a premature infant (34 weeks of gestation). After birth, cerebral infarction was confirmed by magnetic resonance imaging (MRI).

Neurological function of immature babies after surfactant replacement therapy.

Surfactant replacement therapy in patients with neonatal respiratory distress syndrome (RDS) is a new therapeutic approach. There is now convincing evidence that the incidence and severity of RDS can be reduced. Surfactant (CUROSURF) was intratracheally applied to a group of fifteen intubated preterm infants with severe RDS (29 +/- 2.

N-acetyl-L-aspartate is a major source of acetyl groups for lipid synthesis during rat brain development.

The function of N-acetyl-L-aspartate (NAA), a predominant substance in the CNS, has not yet been determined. To investigate the possible function of NAA as a lipid precursor [14C]-N-acetyl-L-aspartate (NAA) or [14C]-acetate (AcA) was injected intracerebrally into 8, 15- and 22-day-old rats. These time points were selected because NAA concentration and the activity of the NAA synthetizing enzyme L-aspartate-N-acetyltransferase (ANAT) were low in 8-day-old rats, intermediate in 15-day-old rats and high in 22-day-old rats.

Neuro-Behçet: acute and sequential aspects by MRI and MRS.

Three patients with neuro-Behçet underwent MRI and MRS during acute illness. After therapy, MRI and MRS were performed in 3 and 1 patients, respectively. MRI revealed a marked improvement of the initial lesion in 2, a complete remission in 1 patient.

Adult forms of metachromatic leukodystrophy: clinical and biochemical approach.

The clinical and biochemical characteristics of metachromatic leukodystrophy (MLD), true adult forms and late juvenile forms which are still living at adulthood, are reviewed as they both are observed in adult Neurology and Psychiatry departments. Mental deterioration is often the first symptom, evolving progressively; and dementia finally occurs. The latency before the appearance of neurological objective symptoms may be long and extend for several years.

Brain development: 1H magnetic resonance spectroscopy of rat brain extracts compared with chromatographic methods.

We compared in vitro 1H magnetic resonance spectroscopy (MRS) measurements of rat brain extracts (rats: 2-56 days old) with chromatographic measurements and in a further step also with results of in vitro MRS. The following substances can be reliably measured in brain extracts by in vitro MRS: N-acetylaspartate (NAA), total creatine (Cr), phosphorylethanoloamine (PE), taurine (Tau), glutamate (Glu), glutamine (Gln), gamma-aminobutyrate (GABA) and alanine (Ala). Two different methods of MRS data evaluation compared with chromatographic data on Cr and NAA are shown.

[Energy metabolism of the brain, detected with 31-P magnetic resonance spectroscopy during extracorporeal circulation in the rabbit].

The question of a possible brain damage during open heart surgery using extracorporeal circulation is still a problem, especially in infants with circulatory arrest under deep hypothermia. During the last years Magnetic Resonance Spectroscopy was developed, and with this method we have now a possibility to study brain energy metabolism non-invasively and continuously. Our aim was to develop an animal model (rabbit) for studying brain energy metabolism by 31-P Magnetic Resonance Spectroscopy during extracorporeal circulation.