Predictive Test for Huntington's Chorea

Klawans, H.L.; Paulson, GeorgeW; Barbeau, A.

doi:10.1016/s0140-6736(70)90367-3

Cited by 69 publications

(31 citation statements)

References 2 publications

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“…The connection between dopamine and HD was first suspected when over one-third of asymptomatic relatives of individuals with HD developed dyskinesis in response to L-DOPA (Klawans et al, 1970). Additional biochemical analysis revealed progressive loss of striatal D 1 and D 2 receptors in postmortem HD brains (Joyce et al, 1988;Filloux et al, 1990;Richfield et al, 1991;Glass et al, 2000;Suzuki et al, 2001).…”

Section: Dopaminergic Signaling and Neurodegeneration Of Hd Msnsmentioning

confidence: 99%

“…The connection between dopaminergic signaling and HD was uncovered when over one-third of asymptomatic relatives of individuals with HD developed dyskinesias in response to L-DOPA (Klawans et al, 1970). Since then, an increasing body of experimental evidence has pointed to a potential role for the dopaminergic system in HD (Jakel and Maragos, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Dopaminergic Signaling and Striatal Neurodegeneration in Huntington's Disease

Tang¹,

Chen²,

Liu³

et al. 2007

J. Neurosci.

188

190

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Huntington's disease (HD) is a neurodegenerative disorder caused by polyglutamine (polyQ) expansion in Huntingtin protein (HttWe demonstrated that potentiating effects of dopamine are mediated by D 1 -class dopamine receptors (DARs) and not by D 2 -class DARs. Consistent with in vitro findings, in whole-animal experiments we found that persistent elevation of striatal dopamine levels exacerbated the behavioral motor deficits and MSN neurodegeneration in YAC128 mice. We further discovered that the clinically relevant dopamine pathway inhibitor tetrabenazine alleviated the motor deficits and reduced striatal cell loss in YAC128 mice. Our results suggest that dopamine signaling pathway plays an important role in HD pathogenesis and that antagonists of dopamine pathway such as tetrabenazine or dopamine receptor blockers may have a therapeutic potential for treatment of HD beyond well established "symptomatic" benefit.

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Section: Dopaminergic Signaling and Neurodegeneration Of Hd Msnsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dopaminergic Signaling and Striatal Neurodegeneration in Huntington's Disease

Tang¹,

Chen²,

Liu³

et al. 2007

J. Neurosci.

188

190

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“…L-do pa, which improves the cardinal manifestations of parkinsonism, increas es the abnormal movements in Huntington's chorea [48,49]. Recently typical choreiform movements have been elicited in 3 pre-symptomatic offspring of patients with known Huntington's chorea by the administra tion of L-dopa [50]. These data, including normal striatal dopamine and spinal fluid HVA levels, are felt to be consistent with the hypothesis that an increased sensitivity to dopamine on the part of degenerating neu rons of the striatum underlies the abnormal movements in Huntington's chorea [15].…”

Section: Discussionmentioning

confidence: 99%

Treatment of Choreoathetotic Movements in Chronic Liver Disease with a Dopamine-Blocking Agent Pathophysiologic Implications

O'Neill¹,

Klawans²,

Holmes³

1971

Stereotact Funct Neurosurg

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Acquired hepatocerebral degeneration (AHCD) is a well-defined clinical and neuropathological entity associated with various types of chronic liver disease, and usually related to portal-systemic shunting. Various movement disorders, including choreoathetosis, are commonly seen in AHCD. The frequent neuropathological finding of neuronal degeneration in the striatum (caudate nuclei and putamens) suggested that choreoathetotic movements in AHCD might be caused by dopamine hypersensitivity in striatal receptor sites and that treatment of such movement disorders might be effected by known striatal dopamine-blocking agents of proven benefit in similar movement disorders, e. g. Huntington’s chorea. A patient with documented post-necrotic cirrhosis and portal hypertension who had had a successful portacaval shunt developed signs of AHCD with choreoathetotic movements of the tongue, face, and mouth (linguo-facio-buccal dyskinesia); he was treated with haloperidol, a striatal dopamine-blocking agent, with prompt and sustained cessation of his dyskinesia. Evidence of a normal baseline central dopamine content and of central dopamine blockade after administration of haloperidol was obtained. The implications of these findings and of similar findings in other movement disorders regarding the role of neuro-transmitting agents in the normal individual and in various disease states are discussed, and therapeutic considerations are presented.

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“…Parkinsonism is associated with decreased brain dopamine synthesis (Hornykiewicz, 1963) and one suggested mechanism of Huntington's chorea is increased sensitivity of dopamine receptors (Klawans, Paulson, and Barbeau, 1970). Therefore if folic acid impairs dopamine synthesis, its administration might be expected to exacerbate Parkinsonism and possibly have a beneficial effect on the manifestations of Huntington's chorea.…”

Section: Beforementioning

confidence: 99%

Effect of folic acid by mouth on cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentration

Hunter

Barnes

Curzon

et al. 1971

Journal of Neurology, Neurosurgery & Psychiatry

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SUMMARY Administration of 30 mg folic acid by mouth caused a significant fall in cerebrospinal fluid homovanillic acid concentration in 11 subjects. There was no significant change of 5-hydroxyindoleacetic acid concentration. The fall was less marked in five patients on anticonvulsant medication and failed to reach statistical significance. Neither homovanillic acid nor 5-hydroxyindoleacetic acid concentrations changed significantly when 15 mg folic acid was given in divided dosage for one, two, and four weeks. The effect appeared to be related to the height of serum-folate levels reached and to be independent of cerebrospinal fluid-folate levels, which did not change significantly. Possible mechanisms and their potential therapeutic application are discussed.

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Predictive Test for Huntington's Chorea

Cited by 69 publications

References 2 publications

Dopaminergic Signaling and Striatal Neurodegeneration in Huntington's Disease

Dopaminergic Signaling and Striatal Neurodegeneration in Huntington's Disease

Treatment of Choreoathetotic Movements in Chronic Liver Disease with a Dopamine-Blocking Agent Pathophysiologic Implications

Effect of folic acid by mouth on cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentration

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