Homovanilic acid in Huntington's disease and Sydenham's chorea.

Abstract

SUMMARY Homovanilic acid (HVA) was determined in the lumbar CSF of 12 patients with Huntington's disease and 12 with Sydenham's chorea before and after probenecid administration. The means of HVA concentration (basal and after probenecid) were lower in those with Huntington's disease than in controls, and were even lower in a sub-group characterised by increased tone and slowness of voluntary movement. There was no correlation between CSF HVA values and the severity of abnormal movements, nor with length of the illness and age of the patients with Huntington's disease. The mean basal HVA concentration did not differ from controls in those with Sydenham's chorea but the accumulation with probenecid was significantly lower. These results suggest a decrease in cerebral dopamine release in both forms of chorea.About one third of the homovanilic acid (HVA) derived from the catabolism of dopamine (DA) and released in the striatum enters the CSF in the lateral ventricle.' 2 There is some evidence to suggest that the concentration of this acid metabolite in ventricular CSF, is related to the concentration in the striatum.24 But the concentration of HVA cisternal and lumbar CSF is lower, and the correlation with striatal levels disappears.' 5 6 At least three mechanisms are responsible for the lower HVA levels-lumbar CSF (1) the diffusion of the HVA "jet," (2) the CSF circulation, (3) an active transport mechanism localised in the fourth ventricle and sub-arachnoid space.7-8 This active transport mechanism can be blocked with probenecid, which prevents the efflux of HVA and 5-HIAA from CSF.8-1" There has been considerable variation in the dose and timing of probenecid administration to man.'2"15

Altered Dopamine and Serotonin Metabolism in Motorically Asymptomatic R6/2 Mice

“…Some of the dopaminergic alterations were also seen in non-striatal regions such as hippocampus and frontal cortex, underlining the early aberrant connectivity of dysfunctional frontostriatal circuits in HD [22] . Likewise, several studies reported decreased CSF levels of HVA in HD patients prior to the HTT gene identification [23] , [24] , [25] . Importantly, we showed for the first time that the DA loss was preceded by altered DA metabolism, i.e.…”

Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington’s disease for participants of varying functional disability: a pilot study

“…In an effort to characterize the metabolome, several studies have demonstrated catabolic changes considered as possible biomarkers of progression 16 . Among these, few consistent patterns have emerged, with discrepant data for amino acids [17][18][19][20][21][22][23][24][25][26] , catecholamine metabolites 27,28 , and lipids 23,29,30 . It is not well established how metabolomic changes correlate to clinical outcome measures over the spectrum of early to advanced manifest disease.…”

A child with recurrent episodes of involuntary movements

“…Nevertheless, the results of studies have varied from showing an elevation of HVA to a reduction in accumulation after probenecid administration. 49,50 Autoimmune Hypothesis: An autoimmune hypothesis has been proposed as the underlying mechanism in Sydenham's chorea; that is, after a streptococcal infection in susceptible individuals, antibodies directed against bacterial antigens cross-react (molecular mimicry) with epitopes on neurons of the basal ganglia and possibly frontal lobes causing choreiform movement abnormalities and behavioral disturbances. Evidence supporting an antineuronal hypothesis in Sydenham's chorea is primarily based on studies by Husby and colleagues who used an immunofluorescent antibody technique to detect tissue-specific antibodies; sera were applied to frozen sections of human brain, a secondary conjugated antihuman IgG antibody was added, and the extent of fluorescence was determined.…”