5‐Hydroxyindoleacetic Acid and Homovanillic Acid in Cerebrospinal Fluid of Children with Febrile Convulsions

Giroud, M; Dumas, R; Dauvergne, M.; d’Athis, Philippe; Rochette, Luc; Beley, A; Bralet, J

doi:10.1111/j.1528-1167.1990.tb06303.x

Cited by 44 publications

(16 citation statements)

References 21 publications

(23 reference statements)

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“…The reduced KYNA/kynurenine and KYNA/3-OH-KYN ratios in epilepsy patients are in line with this neurodegeneration hypothesis. These results are indicative of an imbalance between neuroprotective and neurotoxic metabolites in epilepsy patients, and with previous reports showing significantly lower levels of neuroprotective KYNA in children with intractable epilepsy than in healthy controls [21][22][23] .…”

Section: Discussionsupporting

confidence: 66%

Vagus Nerve Stimulation in Refractory Epilepsy: Effects on Pro- and Anti-Inflammatory Cytokines in Peripheral Blood

Majoie

Rijkers

Berfelo

et al. 2010

Neuroimmunomodulation

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Objective: The vagus nerve has important immunological functions that may be relevant for its anticonvulsive action. We postulate that this anticonvulsive action is activated by a shift in the immune system resulting in a reduction of neurotoxic and an increase of neuroprotective tryptophan metabolites. Methods: Eleven patients with refractory epilepsy and 11 controls matched for age and gender were included in this study. The primary outcome measure was a 50% seizure reduction. Other variables were pro-inflammatory cytokines IL-6 and TNF-α, anti-inflammatory cytokine IL-10, cortisol, and the tryptophan metabolites 3-hydroxykynurenine (3-OH-KYN), kynurenic acid (KYNA), kynurenine, serotonin (5-HT) and 5-hydroxyindol acetic acid (5-HIAA). Blood samples were scheduled during baseline, and in week 28 of add-on treatment. Results: IL-6 levels were higher in the responders than in the control group, and decreased after vagus nerve stimulation (VNS), whereas IL-10 was low and increased after VNS. In nonresponders, VNS resulted in an increase of IL-6 plasma levels and in a decrease of IL-10. Cortisol concentrations are higher in the epilepsy group than in the control group. After VNS, these concentrations decreased. The concentrations of the tryptophan metabolites were lower in the epilepsy group than in the control group. The KYNA ratios are defined as the ratio of neuroprotective KYNA versus neurotoxic 3-OH-KYN and KYNA versus neurotoxic kynurenine: these ratios were lower in epilepsy patients than in controls, and they both moderately increased after VNS. Conclusion: The outcome of this preliminary study indicates that VNS causes a rebalancing of the immune system. This results in: (1) a reduction of neurotoxic and an increase of neuroprotective kynurenine metabolites and (2) in the normalization of cortisol levels.

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Section: Discussionsupporting

confidence: 66%

Vagus Nerve Stimulation in Refractory Epilepsy: Effects on Pro- and Anti-Inflammatory Cytokines in Peripheral Blood

Majoie

Rijkers

Berfelo

et al. 2010

Neuroimmunomodulation

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“…Controversial results for HVA concentrations in the CSF in different types of epilepsy have been reported. 16,17 A decreased concentration of HVA in adults with complex partial seizures but normal in patients with generalized tonic-clonic seizures has also been described. 5 Van der Heyden et al 4 also reported a strong association between low HVA and epilepsy (the patients suffered from different types of epilepsy, many of them in combination with another neurological disorder); however, the age range of these patients was very large.…”

Section: (2) Neurological Patternmentioning

confidence: 99%

Secondary abnormalities of neurotransmitters in infants with neurological disorders

García‐Cazorla

Serrano

Pérez‐Dueñas

et al. 2007

Develop Med Child Neuro

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Neurotransmitters are essential in young children for differentiation and neuronal growth of the developing nervous system. We aimed to identify possible factors related to secondary neurotransmitter abnormalities in pediatric patients with neurological disorders. We analyzed cerebrospinal fluid (CSF) and biogenic amine metabolites in 56 infants (33 males, 23 females; mean age 5.8mo [SD 4.1mo] range 1d-1y) with neurological disorders whose aetiology was initially unknown. Patients were classified into three clinical phenotypes: epileptic encephalopathy, severe motor impairment, and non-specific manifestations. All patients showed normal results for screening of inborn errors of metabolism. We report clinical, neuroimaging, and follow-up data. Among the patients studied, 10 had low homovanillic acid (HVA) levels and in four patients, 5-hydroxyindoleacetic acid (5-HIAA) was also reduced. Patients with neonatal onset had significantly lower levels of HVA than a comparison group. HVA deficiency was also associated with severe motor impairment and the final diagnosis related to neurodegenerative disorders. 5-HIAA values tended to be decreased in patients with brain cortical atrophy. The possibility of treating patients with L-Dopa and 5-hydroxytryptophan, in order to improve their neurological function and maturation, may be considered.Brain neurotransmission is essential in young children, not only for interneuronal communication but also for differentiation, neuronal growth, and shaping and wiring of the nervous system. 1 Biogenic amines are the most representative group among brain neurotransmitters 2 and are composed of catecholamines (dopamine and norepinephrine) and serotonin. Within the central nervous system, the final metabolite for dopamine is homovanillic acid (HVA) and for serotonin, 5-hydroxyindoleacetic acid (HIAA). These metabolites can be measured in the cerebrospinal fluid (CSF). Low concentrations of biogenic amine metabolites in the CSF are mainly due to defects in their biosynthetic and catabolic pathways. Deficiencies of tyrosine hydroxylase, aromatic L-amino acid decarboxylase, guanosine triphosphate cyclohydrolase (GTPCH), and sepiapterin reductase, 3 (the last two enzymes contributing to the formation of tetrahydrobiopterin [BH4]), cause the main paediatric neurotransmitter diseases.Little is known about secondary causes of low CSF biogenic amine metabolites, and, to our knowledge, no study focusing on how diverse neurological disorders in infants could affect brain biogenic amines production has been described until now. There are a few studies that have looked at secondary reduction of HVA. It has been reported that epilepsy, 4,5 rapidonset dystonia-parkinsonism, 6 Huntington's disease, 7 and depression and dementia 8,9,10 are among those disorders characterized by secondary reduction of HVA. However, the results found in these studies are often contradictory and not specific to young children. Moreover, no study concerning possible factors that could be related to these secondary abnormalit...

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“…Both experimental and clinical observations suggest that changes in levels of 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylacetic acid [homovaniliic acid (HVA)] in the CSFand in the brain may be a biological marker of pathological brain activity. Among monoamine metabolites, 5-HIAA and HVA are changed in concentration in patients with various types of seizures (Giroud et al, 1990), obsessive-compulsive disorders (Insel et al, 1989, hepatic encephalopathy (Knell et al, 1974Jellinger et al, 1978;Moroni et al, 1986), and hypoxic brain injury after cardiac arrest (Odink et al, 1989). 5-HIAA and HVA levels were increased in a doserelated manner by 2,4-dichlorophenoxyacetic acid experimentally in rat CSF and brain (Elo and Mac-Donald, 1989).…”

mentioning

confidence: 99%

Octanoic Acid Produces Accumulation of Monoamine Acidic Metabolites in the Brain: Interaction with Organic Anion Transport at the Choroid Plexus

Kim

Roe

Mann

et al. 1992

Journal of Neurochemistry

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Effects of octanoic acid on monoamines and their acidic metabolites in the rat brain were analyzed by HPLC. Octanoic acid (1,000 mg/kg i.p.) elevated homovanillic acid levels by 54% in the caudate and 338% in the hypothalamus but increased 5-hydroxyindoleacetic acid (5-HIAA) levels in both the caudate and the hypothalamus by approximately 50% compared with the control. A lower dose of octanoic acid (500 mg/kg) increased 5-HIAA levels by 29% in the caudate and 20% in the hypothalamus. However, it did not produce any changes in the concentration of homovanillic acid in either the caudate or the hypothalamus. Treatment with octanoic acid also failed to change the level of dopamine, serotonin, and 3,4-dihydroxyphenylacetic acid in the caudate and the hypothalamus. The role of carrier-mediated transport in the clearance of 5-HIAA from the rabbit CSF was also evaluated in vivo by ventriculocisternal perfusion. Steady-state clearance of 5-HIAA from CSF exceeded that of inulin and was reduced in the presence of octanoic acid. Because this transport system in the choroid plexus is normally responsible for the excretion of the serotonin metabolite from the brain to the plasma, accumulation of endogenously produced organic acids in the brain, secondary to reduced clearance by the choroid plexus, could be a contributing factor in the development of encephalopathy in children with medium-chain acyl-CoA dehydrogenase deficiency who have elevated levels of octanoic acid systematically.

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5‐Hydroxyindoleacetic Acid and Homovanillic Acid in Cerebrospinal Fluid of Children with Febrile Convulsions

Cited by 44 publications

References 21 publications

Vagus Nerve Stimulation in Refractory Epilepsy: Effects on Pro- and Anti-Inflammatory Cytokines in Peripheral Blood

Vagus Nerve Stimulation in Refractory Epilepsy: Effects on Pro- and Anti-Inflammatory Cytokines in Peripheral Blood

Secondary abnormalities of neurotransmitters in infants with neurological disorders

Octanoic Acid Produces Accumulation of Monoamine Acidic Metabolites in the Brain: Interaction with Organic Anion Transport at the Choroid Plexus

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