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Biogenic Amine Metabolites and Thiamine in Cerebrospinal Fluid in Heredo-Degenerative Ataxias

  • M.I. Botez (a1) and S.N. Young (a1)



The aims of the present study were: i) to measure levels of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxindoleacetic acid (5HIAA) and precursor tryptophan, as well as the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and thiamine in the cerebrospinal fluid (CSF) of patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA), and the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSAC), as compared with sex- and age-matched control subjects.

Patients and methods:

CSF amine related compound levels and thiamine results were compared in 40 FA, 44 OPCAand nine ARSAC patients with those of 94 sex- and age-matched subjects. Neuroimaging (CT scans and single photon emission computed tomographies i.e. SPECT) were carried out in all patients and controls. Genetic studies were conducted on OPCApatients. CSF amine related compounds were measured by high performance liquid chromatography, whereas CSF thiamine levels were measured by a microbiological method.


FA patients had significantly lower CSF HVA, 5HIAA and thiamine values than control patients and a trend for lower MHPG levels. In OPCA patients, CSF HVA, MHPG and thiamine values were markedly lower whereas CSF 5HIAA values showed only a trend towards lower levels; in ARSAC patients only thiamine and HVA CSF values were lower than those in control subjects.


After presenting the relationships between neurochemical findings on one side, the degree of ataxia, the degree of cerebellar atrophy and the SPECT findings on the other, the authors concluded that replacement and neuroprotective clinical trials in these patients would have to include two or three drugs because the neurotransmitter deficiencies are multiple.

RÉSUMÉ: Introduction:

Les buts de cette étude étaient de mesurer les niveaux d'acide homovanillique (HVA), un métabolite de la dopamine, d'acide 5-hydroxindoleacétique (5HIAA) , un métabolite de la sérotonine, et de son précurseur, le tryptophane, ainsi que du 3-méthoxy-4-hydroxyphényléthylène glycol (MHPG), un métabolite de la noradrénaline et de la thiamine dans le liquide céphalorachidien (LCR) de patients atteints d'ataxie de Friedreich (AF), d'atrophie olivopontocérébelleuse (OPCA) et d'ataxie spastique autosomale récessive de Charlevoix-Saguenay (ARSAC) et de les comparer à ceux de sujets contrôles appariés pour le sexe et l'âge.

Patients et méthodes:

Les niveaux de composés reliés aux amines du LCR et les résultats de thiamine ont été comparés chez 40 patients atteints d'AF, 44 d'OPCAet neuf d'ARSAC à ceux de 94 sujets contrôles appariés pour le sexe et l'âge. Des examens de neuroimagerie (CT scan et tomographie à émetteur gamma i.e. SPECT) ont été effectués chez tous les patients et les contrôles. Les patients atteints d'OPCA ont également subi des tests génétiques. Les composés reliés aux amines du LCR ont été mesurés par chromatographie à haute pression en phase liquide et les niveaux de thiamine ont été mesurés par une méthode microbiologique.


Les patients atteints d'AF avaient des valeurs de HVA, de 5HIAAet de thiamine du LCR significativement plus basses que les sujets contrôles et une tendance à des niveaux plus bas de MHPG. Chez les patients atteints d'OPCA, les valeurs de HVA, de MHPG et de thiamine du LCR étaient beaucoup plus basses, alors que les valeurs de 5HIAAdu LCR avaient seulement une tendance à être plus basses; chez les patients atteints d'ARSAC, seulement les valeurs de thiamine et de HVA du LCR étaient plus basses que celles des sujets contrôles.


Les auteurs présentent les relations entre les observations neurochimiques d'une part et le degré d'ataxie et d'atrophie cérébelleuse et les observations de neuroimagerie d'autre part et ils concluent que les essais thérapeutiques de remplacement et de neuroprotection chez ces patients devraient inclure deux ou trois médicaments à cause des déficits multiples en neurotransmetteurs.

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Corresponding author

Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montréal, Québec, Canada H3A1A1


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