Psychosocial stress and severe prematurity.
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Denmark↗
Biomedical subjects
H C Lou
Publications and source records attributed to H C Lou.
An occipito-temporal syndrome in adolescents with optimally controlled hyperphenylalaninaemia.
The study included 16 adolescents with optimally controlled hyperphenylalaninaemia (McKusick 26160), of whom six did not require treatment according to conventional criteria. All except the two patients with lowest median serum phenylalanine level throughout childhood (most values at 200-300 mumol/L) had white matter abnormalities detectable with magnetic resonance imaging. The lesions were particularly prominent in the watershed regions between the posterior and middle cerebral arteries. In most patients with moderate or severe hyperphenylalaninaemia frontal white matter lesions were present as well. Normal proton magnetic resonance spectra indicated that the lesions were stable. Occipital EEG abnormalities were frequent, and deficient performance on a pattern-recognition test was a characteristic neuropsychological finding. Serum phenylalanine levels at about 300 mumol/L or below throughout childhood and early adolescence may be required to avoid lesions. The present study demonstrates the limitations of even an optimally controlled dietary regimen in hyperphenylalaninaemia.
Adolescent↗
Low CSF HVA levels in the Rett syndrome: a reflection of restricted synapse formation?
The concentration of neurotransmitter metabolites in the CSF was determined in 10 girls with the Rett syndrome (RS) (age range 5.8-17.2) and in 14 control children (age range 4.5-16.7) treated for acute leukemia without signs of CNS involvement. Homovanillic acid concentration decreased with age in both groups. The decrease was less steep in RS compared to controls, with lower concentrations in young girls and normal concentrations at 15 years of age. 5-hydroxyindoleacetic acid decreased proportionally in both groups. It is suggested that the low concentration of HVA in young girls reflect deficient multiplication of catecholaminergic synapsis.
Adolescent↗
Focal cerebral dysfunction in developmental learning disabilities.
In 24 children with developmental learning disabilities and 15 age-matched controls regional cerebral activity was studied with xenon-133 single photon emission tomography. In the 9 children with pure attention deficit and hyperactivity disorder (ADHD), the distribution of regional cerebral activity was abnormal--low in striatal and posterior periventricular regions and high in occipital regions. Low activity in striatal and posterior periventricular areas was also seen in the 8 children with ADHD in combination with phonologic-syntactic dysphasia. 7 children with dysphasia, but without hyperactive behaviour, had low cerebral activity in left temporofrontal regions.
Adolescent↗
Biochemical and clinical effects of tyrosine and tryptophan in the Rett syndrome.
In the Rett syndrome (RS), a progressive encephalopathy affecting girls, deficient neurotransmitter synthesis has been suggested as a pathogenetic mechanism. Nine girls with RS were treated with 0.3 g of tyrosine and 0.1 g of tryptophan per kg body weight for 2 to 17 weeks. This resulted in a median rise in the spinal fluid concentration of the dopamine metabolite homovanillic acid by 31%, and of the serotonin metabolite 5-hydroxyindoleacetic acid by 40%. This finding supports the hypothesis of a compromised neurotransmitter synthesis and indicates that it can be stimulated by supply of amino acid precursors. A double-blind cross-over trial including 11 girls did not show clinical improvement during a treatment period of 8 to 10 weeks.
Adolescent↗
Striatal dysfunction in attention deficit and hyperkinetic disorder.
We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD.
Attention Deficit Disorder with Hyperactivity↗
Flunarizine in paroxysmal choreoathetosis.
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Child↗
Intellectual impairment with regional cerebral dysfunction after low neonatal cerebral blood flow.
12 children, in whom neonatal CBF had been measured, were examined at the age of 9 to 10 years by means of clinical neurological examination, neuropsychologic tests and observations, and 133Xe single photon emission computed tomography (SPECT). Performance on most neuropsychologic tests or observations correlated with neonatal CBF but only rarely with other neonatal parameters (birthweight, gestational age, Apgar score at 5 min). Poor performance on each test or observation was in most instances correlated with a distinct pattern of regional cerebral dysfunction as assessed by SPECT. The dysfunctional region tended to be located periventricularly and in the watershed regions between major cerebral arteries. It is concluded that low neonatal cerebral perfusion may be an indicator, and possibly a determinant, of later intellectual dysfunction in stressed neonates, and that specific neuropsychologic deficits are associated with specific patterns of cerebral dysfunction in the present patient group.
Brain Diseases↗
Endogenous opioids may protect the perinatal brain in hypoxia.
Endogenous opioids are released in great amounts in perinatal asphyxia. The role of this release has been unclear. In a study of cerebral blood flow and oxygen metabolism in 5 hypoxic newborn lambs, naloxone blocking of opioid receptors resulted in a proportional increase in telencephalic cerebral blood flow and oxygen metabolism. It is suggested that endogenous opioid release protects the neonatal brain in hypoxia by diminishing the cerebral metabolic rate of oxygen.
Animals↗
Increased neurotransmitter biosynthesis in phenylketonuria induced by phenylalanine restriction or by supplementation of unrestricted diet with large amounts of tyrosine.
Seven phenylketonuria (PKU) patients aged 15-24 years were allowed unrestricted diet for 3 weeks. Three of these patients performed well on unrestricted diet according to visual reaction time variability (RTv 50-100 ms) and did not show significant changes when returning to the phenylalanine-restricted diet (RTv 70-100 ms). Neither did the concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) change significantly. Four of the patients, however, performed rather poorly (RTv 120-220 ms) on unrestricted diet and improved significantly (P less than 0.03) when the diet was restored (RTv 70-150 ms). The improvements were accompanied by significant (P less than 0.01 and P less than 0.02) increases (mean 52% and 109%) in CSF levels of HVA and 5-HIAA. Five PKU patients aged 15-23 years were allowed unrestricted diet or unrestricted diet supplemented with various amounts of tyrosine (106-194 mg/kg per 24 h). Two of these patients performed very well on unrestricted diet (RTv 60 ms) and showed little change when the unrestricted diet was supplemented with tyrosine (RTv 70 ms and 80 ms). The three other patients, who performed rather poorly (RTv 120-220 ms), improved significantly (P less than 0.03) when the unrestricted diet was supplemented with tyrosine (RTv 70-140 ms). HVA in CSF increased significantly (P less than 0.01) with the tyrosine supplement when the amount exceeded a threshold of approximately 80 mg/kg per 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
The "lost autoregulation hypothesis" and brain lesions in the newborn--an update.
Autoregulation of cerebral blood flow is an essential homeostatic mechanism which is easily disturbed during the stresses in the birth process. In its absence, moderate hypotension, a frequent complication in neonatal asphyxia, may induce cerebral ischemia, the arterial watershed zones in periventricular regions being particularly prone. The initial ischemia in perinatal stress produces functional disturbance (EEG depression), which is not readily reversible as the circulation improves. Hypotension, cerebral hypoperfusion and EEG depression precedes severe periventricular hemorrhage, which seems to be triggered by fluctuations in arterial blood pressure and flow, with fluctuations in the transmural pressure gradient across the capillary wall. The penetration of the hemorrhaging into surrounding brain tissue is related to the magnitude of the preceding ischemic insult.
Animals↗
Perinatal hypoxic-ischaemic brain damage and intraventricular haemorrhage.
It is now apparent that the principal lesions of perinatal asphyxia--cerebral hypoxic-ischaemic damage and IVH--are pathogenetically interrelated, a fact that has long been suspected by pathologists (Pape and Wigglesworth, 1979). Prevention of such lesions would require, on the one hand, circulatory support to prevent hypotension and, on the other hand, the means to avoid excessive arterial pressure peaks in the early neonatal period together with experimental and clinical research to determine the optimal PCO2 level. It may therefore be concluded that neonatal ischaemia is a critical determinant for later neurological and intellectual development, and is probably the most important single factor known at present. Our consistent finding of hypoperfusion and, by inference, low metabolic activity supports the hypothesis that this ischaemia may cause minor structural changes in the white matter border zones between major arterial territories, leading to severe learning disorders in these children, who were examined with the 133Xe-inhalation computerized emission tomography technique (Lou et al, 1984).
Asphyxia Neonatorum↗
The concept of coupling blood flow to brain function: revision required?
A tight coupling exists between brain function and cerebral perfusion in most situations. The Roy and Sherrington hypothesis has been widely accepted to account for the phenomenon: increased neuronal metabolic activity will give rise to the accumulation of vasoactive catabolites, which decrease vascular resistance and thereby increase blood flow until normal homeostasis is reestablished. However, the hypothesis does not account for the disproportionate increase in flow that occurs in a number of circumstances. There are additional difficulties in reconciling more recent experimental data with the Roy and Sherrington hypothesis. In this review we direct attention toward the rich perivascular nerve supply to all parts of the cerebral circulation as possibly being an alternative control system allowing for rapid parallel changes in flow and neuronal activity.
Animals↗
Increased vigilance and dopamine synthesis by large doses of tyrosine or phenylalanine restriction in phenylketonuria.
In a group of 9 patients with classical phenylketonuria (PKU) aged 15-24 years we examined the effect of phenylalanine restricted diet on vigilance, as judged by the continuous visual reaction times, and neurotransmitter synthesis, as judged by cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) levels. HVA and 5-HIAA levels decreased significantly with increase in plasma phenylalanine concentration on free diet (p less than 0.01 and p less than 0.0005 respectively). Vigilance improved on phenylalanine restricted diet in 6 of the 7 patients with abnormally long reaction times on free diet. Addition of tyrosine (160 mg/kg/24 h) to the free diet resulted in an increased CSF in the six patients examined. In 14 patients on free diet supplemented with tyrosine, an improvement in vigilance (reaction times at the 90 percentile) was seen in all 12 patients with values longer than the normal mean (264 msec) (p less than 0.001). Tyrosine treatment may be a therapeutical alternative when phenylalanine restriction is impractical.
Adolescent↗
On the pathogenesis of regional cerebral ischemia in intracranial hemorrhage: a causal influence of potassium?
Cerebral ischemia and intracranial hemorrhage are the most important causes of perinatal brain damage and their pathogenesis seems to be interrelated. Several components in blood have been shown to cause contraction of cerebral blood vessels. In the present study we examined the changes with time of the concentration of standard electrolytes in a mixture of blood and mock cerebrospinal fluid, whether these changes may affect cerebrovascular tone, and if calcium blockers could influence such an effect. Extracellular K+ increased to about 23 mM 4 days after mixing when half of the mixture consisted of blood, and remained nearly constant for at least 8 days thereafter. Using isometric recording of circular tension in a controlled tissue bath it was found that isolated human pial arterioles, small arteries, and feline middle cerebral arteries contracted markedly when K+ exceeded 10 and 20 mM, respectively. It is concluded that neonatal perihemorrhagic ischemia may be, at least partly, due to leakage of K+ from the erythrocytes. The contractile effect of extracellular K+ is effectively counteracted by Ca++ entry blockers, which therefore may have a role in the prevention of perihemorrhagic ischemia in neonates.
Animals↗
Preferential blood flow increase to the brain stem in moderate neonatal hypoxia: reversal by naloxone.
Previous studies have shown that severe neonatal asphyxia and hypoxia lead to a redistribution of cerebral blood flow (CBF) with a preferential perfusion of the brain stem. The present study shows that this mechanism is operative also in moderately hypoxic newborn lambs (oxygen saturation 32.7-65.2) with a threshold of about 25% reduction in oxygen saturation. In hypoxia, the mean increase in total CBF, brain stem and telencephalic blood flow was 44%, 68% and 43%, respectively (five lambs). We found that naloxone reverses this redistribution, and that the effects of naloxone on telencephalic perfusion and cerebral metabolic rate of oxygen (CMRO2) were proportional. In hypoxia + naloxone (1 mg/kg), a further increase in total CBF, brain stem, and telencephalic blood flow of 30%, 7% and 31% was noted. We therefore suggest that the redistribution of CBF is an important opioid-mediated homeostatic mechanism, which diminishes the metabolic requirements of the newer part of the brain in hypoxia and allows a preferential perfusion of the vital structures of the brain stem.
Animals↗
Decreased vigilance and neurotransmitter synthesis after discontinuation of dietary treatment for phenylketonuria in adolescents.
Four adolescent or young adult patients with phenylketonuria were examined before and after discontinuation of dietary treatment. Plasma and CSF phenylalanine concentrations increased about two-fold in three patients. In these patients the CSF concentration of the dopamine and serotonin metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) decreased markedly; 5-HIAA to extremely low values. The reaction time variability increased in these patients. In the fourth case plasma phenylalanine levels, CSF HVA and 5-HIAA levels, and reaction time variability were essentially unchanged. The relationship between reaction time variability and the CSF 5-HIAA level for all four patients could be presented as a linear function. However, a causal relationship is still unproven. These preliminary findings demonstrate that there may be hazards in the discontinuation of dietary treatment, even in adolescents or young adults, for neurotransmitter metabolism and mental function.
Adolescent↗
Biopterin, neopterin and tyrosine responses to combined oral phenylalanine and tetrahydrobiopterin loading tests in two normal children and in a girl with partial biopterin deficiency.
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Administration, Oral↗