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CSF Monoamine Metabolites in Movement Disorders and Normal Aging

Stephen M. Stahl, MD, PhD; Kym F. Faull, PhD; Jack D. Barchas, MD; Philip A. Berger, MD
[+] Author Affiliations

Accepted for publication March 22, 1984.

Reprint requests to Psychiatry Service 4B2, VA Medical Center, 3801 Miranda Ave, Palo Alto, CA 94304 (Dr Stahl).


Arch Neurol. 1985;42(2):166-169. doi:10.1001/archneur.1985.04060020080021
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• We measured four monoamine metabolite levels in CSF before and after probenecid administration to normal controls and to patients with Huntington's disease (HD), dystonia, and tardive dyskinesia. We identified differences only for the dopamine metabolite homovanillic acid (HVA), which showed increased baseline values and decreased turnover in normal aging, but decreased baseline values and normal turnover in HD. These results suggest that dopamine neurons are linked both to normal aging and to HD and that CSF HVA studies can distinguish differences in the functioning of dopamine neurons in normal aging and HD.

REFERENCES

Guilleminault C, Tharp BR, and Cousin D:  HVA and 5HIAA CSF measurements and 5HTP trials in some patients with involuntary movements . Neurol Sci 1973;;18:435-441.
Davidson DLW, Yates CM, Mawdsley C, et al:  CSF studies on the relationship between dopamine and 5-hydroxy-tryptamine in parkinsonism and other movement disorders . J Neurol Neurosurg Psychiatry 1977;;40:1136-1141.
Papeschi R, Molina-Negro P, Sourkes TL, et al:  The concentration of homovanillic and 5-hydroxyindoleacetic acids in ventricular and lumbar CSF: Studies in patients with extrapyramidal disorders, epilepsy, and other diseases . Neurology 1972;;22:1151-1159.
Gottfries CG, Gottfries I, Johansson B, et al:  Acid monoamine metabolites in human cerebrospinal fluid and their relations to age and sex . Neuropharmacology 1971;;10:665-672.
Bowers M, Gerbode FA:  Relationship of monoamine metabolites in human cerebrospinal fluid to age . Nature 1968;;219:1256-1257.
Faull KF, Kraemer HC, Barchas JD, et al:  Clinical application of the probenecid test for measurement of monamine turnover in the CNS . Biol Psychiatry 1981;;16:879-899.
Bowers MB:  Clinical measurements of central dopamine and 5-hydroxytryptamine metabolism: Reliability and interpretation of cerebrospinal fluid acid monoamine metabolite measures . Neuropharmacology 1972;;11:101-111.
Stahl SM, Berger PA:  Bromocriptine, physostigmine and neurotransmitter mechanisms in the dystonias . Neurology 1982;;32:889-892.
Faull KF, Anderson PJ, Barchas JD, et al:  A selected ion monitoring assay for biogenic amine metabolites and probenecid in human lumbar cerebrospinal fluid . J Chromatogr 1972;;163:337-349.
Berger PA, Faull KF, Kilkowski J, et al:  CSF monoamine metabolites in schizophrenia and depression . Am J Psychiatry 1980;;137:174-180.
Caraceni T, Calderini G, Consolazione A, et al:  Biochemical aspects of Huntington's chorea . J Neurol Neurosurg Psychiatry 1977;;40:581-587.
Chase TN:  Biochemical and pharmacologic studies of monamines in Huntington's chorea , in Barbeau A, Chase TN, Paulson GW (eds): Huntington's Chorea, 1872-1972: Advances in Neurology . New York, Raven Press, 1973;, vol 1, pp 533-542.
Curzon G, Gumpert J, Sharpe D:  Amine metabolites in the cerebrospinal fluid in Huntington's chorea . J Neurol Neurosurg Psychiatry 1973;;21:1337-1340.
Shista SK, Templer DI:  Cerebrospinal fluid amine metabolic end-products: Biochemical correlates of intelligence . Res Commun Chem Pathol Pharmacol 1975;;12:601-604.
Klawans HL:  Cerebrospinal fluid homovanillic acid in Huntington's chorea . J Neurol Sci 1971;;13:277-279.
Yates CM, Magill BE, Davidson D, et al:  Lysosomal enzymes, amino acids, and acid metabolites of amines in Huntington's chorea . Clin Chim Acta 1973;;44:139-145.
Mattsson B, Persson SA:  Cerebrospinal homovanillic acid and 5-hydroxyindole acetic acid in Huntington's chorea . Acta Psychiatry Scand 1974;;255( (suppl) ):245-259.
Chase TN, Wexler NS, Barbeau A (eds): Huntington's Disease. Advances in Neurology . New York, Raven Press, 1979;, vol 23.
Bird ED:  Chemical pathology of Huntington's disease . Ann Rev Pharmacol Toxicol 1980;;20:533-551.
Spokes EGS:  Dopamine in Huntington's disease: A specific study of postmortem brain tissue , in Chase TN, Wexler NS, Barbeau A (eds): Huntington's Disease: Advances in Neurology . New York, Raven Press, 1979;, vol 23, pp 481-493.
Cowdry RW, Ebert MH, van Kammen DP, et al:  Cerebrospinal fluid probenecid studies: A reinterpretation . Biol Psychiatry 1983;;18:1287-1299.
Wode-Helgodt B, Sedvall G:  Correlations between height of subject and concentrations of monoamine metabolites in cerebrospinal fluid from psychotic men and women . Commun Psychopharmacol 1978;;2:177-183.
Siever L, Kraemer H, Sack R, et al:  Gradients of biogenic amine metabolites in cerebrospinal fluid . Dis Nerv Syst 1975;;36:13-16.
Eldridge R, Fahn S (eds): Dystonia: Advances in Neurology . New York, Raven Press, 1976;, vol 14.
Fann WE, Smith RC, Davis JM, et al (eds): Tardive Dyskinesia: Research and Treatment . New York, SP Medical & Scientific Books, 1980;.
Baldessarini RJ, Tarsy D:  The pathophysiologic basis of tardive dyskinesia , in Fann WE, Smith RC, Davis JM, et al (eds): Tardive Dyskinesia: Research and Treatment . New York, SP Medical & Scientific Books, 1980;, pp 181-186.
Pind K, Faurbye A:  Concentration of homovanillic acid and 5-hydroxyindoleacetic acid in the cerebrospinal fluid after treatment with probenecid in patients with drug-induced tardive dyskinesia . Acta Psychiatr Scand 1970;;46:323-326.
Nagao T, Ohshimo T, Mitsunobu K, et al:  Cerebrospinal fluid monoamine metabolites and cyclic nucleotides in chronic schizophrenic patients with tardive dyskinesia or drug-induced tremor . Biol Psychiatry 1979;;14:509-523.
Chase TN, Gordon EK, Ng LKY:  Norepinephrine metabolism in the central nervous system of man: Studies using 3-methoxy-4-hydroxy-phenylethylene glycol levels in cerebrospinal fluid . J Neurochem 1973;;21:581-587.
Curzan G:  Involuntary movements other than parkinsonism: Biochemical aspects . Proc R Soc Med 1973;;66:873-876.
Lal S, Allen J, Etienne P, et al:  Dopaminergic function in Gilles de la Tourette's syndrome, Sydenham's chorea and torsion dystonia . Clin Neurol Neurosurg 1976;;79:66-69.
Tabaddor K, Wolfson LI, Sharpless NS:  Diminished ventricular fluid dopamine metabolites in adult-onset dystonia . Neurology 1978;;28:1254-1258.
Wolfson LI, Sharpless NS, Thal LJ, et al:  Decreased ventricular fluid norepinephrine metabolite in childhood-onset dystonia . Neurology 1983;;33:369-372.

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Guilleminault C, Tharp BR, and Cousin D:  HVA and 5HIAA CSF measurements and 5HTP trials in some patients with involuntary movements . Neurol Sci 1973;;18:435-441.
Davidson DLW, Yates CM, Mawdsley C, et al:  CSF studies on the relationship between dopamine and 5-hydroxy-tryptamine in parkinsonism and other movement disorders . J Neurol Neurosurg Psychiatry 1977;;40:1136-1141.
Papeschi R, Molina-Negro P, Sourkes TL, et al:  The concentration of homovanillic and 5-hydroxyindoleacetic acids in ventricular and lumbar CSF: Studies in patients with extrapyramidal disorders, epilepsy, and other diseases . Neurology 1972;;22:1151-1159.
Gottfries CG, Gottfries I, Johansson B, et al:  Acid monoamine metabolites in human cerebrospinal fluid and their relations to age and sex . Neuropharmacology 1971;;10:665-672.
Bowers M, Gerbode FA:  Relationship of monoamine metabolites in human cerebrospinal fluid to age . Nature 1968;;219:1256-1257.
Faull KF, Kraemer HC, Barchas JD, et al:  Clinical application of the probenecid test for measurement of monamine turnover in the CNS . Biol Psychiatry 1981;;16:879-899.
Bowers MB:  Clinical measurements of central dopamine and 5-hydroxytryptamine metabolism: Reliability and interpretation of cerebrospinal fluid acid monoamine metabolite measures . Neuropharmacology 1972;;11:101-111.
Stahl SM, Berger PA:  Bromocriptine, physostigmine and neurotransmitter mechanisms in the dystonias . Neurology 1982;;32:889-892.
Faull KF, Anderson PJ, Barchas JD, et al:  A selected ion monitoring assay for biogenic amine metabolites and probenecid in human lumbar cerebrospinal fluid . J Chromatogr 1972;;163:337-349.
Berger PA, Faull KF, Kilkowski J, et al:  CSF monoamine metabolites in schizophrenia and depression . Am J Psychiatry 1980;;137:174-180.
Caraceni T, Calderini G, Consolazione A, et al:  Biochemical aspects of Huntington's chorea . J Neurol Neurosurg Psychiatry 1977;;40:581-587.
Chase TN:  Biochemical and pharmacologic studies of monamines in Huntington's chorea , in Barbeau A, Chase TN, Paulson GW (eds): Huntington's Chorea, 1872-1972: Advances in Neurology . New York, Raven Press, 1973;, vol 1, pp 533-542.
Curzon G, Gumpert J, Sharpe D:  Amine metabolites in the cerebrospinal fluid in Huntington's chorea . J Neurol Neurosurg Psychiatry 1973;;21:1337-1340.
Shista SK, Templer DI:  Cerebrospinal fluid amine metabolic end-products: Biochemical correlates of intelligence . Res Commun Chem Pathol Pharmacol 1975;;12:601-604.
Klawans HL:  Cerebrospinal fluid homovanillic acid in Huntington's chorea . J Neurol Sci 1971;;13:277-279.
Yates CM, Magill BE, Davidson D, et al:  Lysosomal enzymes, amino acids, and acid metabolites of amines in Huntington's chorea . Clin Chim Acta 1973;;44:139-145.
Mattsson B, Persson SA:  Cerebrospinal homovanillic acid and 5-hydroxyindole acetic acid in Huntington's chorea . Acta Psychiatry Scand 1974;;255( (suppl) ):245-259.
Chase TN, Wexler NS, Barbeau A (eds): Huntington's Disease. Advances in Neurology . New York, Raven Press, 1979;, vol 23.
Bird ED:  Chemical pathology of Huntington's disease . Ann Rev Pharmacol Toxicol 1980;;20:533-551.
Spokes EGS:  Dopamine in Huntington's disease: A specific study of postmortem brain tissue , in Chase TN, Wexler NS, Barbeau A (eds): Huntington's Disease: Advances in Neurology . New York, Raven Press, 1979;, vol 23, pp 481-493.
Cowdry RW, Ebert MH, van Kammen DP, et al:  Cerebrospinal fluid probenecid studies: A reinterpretation . Biol Psychiatry 1983;;18:1287-1299.
Wode-Helgodt B, Sedvall G:  Correlations between height of subject and concentrations of monoamine metabolites in cerebrospinal fluid from psychotic men and women . Commun Psychopharmacol 1978;;2:177-183.
Siever L, Kraemer H, Sack R, et al:  Gradients of biogenic amine metabolites in cerebrospinal fluid . Dis Nerv Syst 1975;;36:13-16.
Eldridge R, Fahn S (eds): Dystonia: Advances in Neurology . New York, Raven Press, 1976;, vol 14.
Fann WE, Smith RC, Davis JM, et al (eds): Tardive Dyskinesia: Research and Treatment . New York, SP Medical & Scientific Books, 1980;.
Baldessarini RJ, Tarsy D:  The pathophysiologic basis of tardive dyskinesia , in Fann WE, Smith RC, Davis JM, et al (eds): Tardive Dyskinesia: Research and Treatment . New York, SP Medical & Scientific Books, 1980;, pp 181-186.
Pind K, Faurbye A:  Concentration of homovanillic acid and 5-hydroxyindoleacetic acid in the cerebrospinal fluid after treatment with probenecid in patients with drug-induced tardive dyskinesia . Acta Psychiatr Scand 1970;;46:323-326.
Nagao T, Ohshimo T, Mitsunobu K, et al:  Cerebrospinal fluid monoamine metabolites and cyclic nucleotides in chronic schizophrenic patients with tardive dyskinesia or drug-induced tremor . Biol Psychiatry 1979;;14:509-523.
Chase TN, Gordon EK, Ng LKY:  Norepinephrine metabolism in the central nervous system of man: Studies using 3-methoxy-4-hydroxy-phenylethylene glycol levels in cerebrospinal fluid . J Neurochem 1973;;21:581-587.
Curzan G:  Involuntary movements other than parkinsonism: Biochemical aspects . Proc R Soc Med 1973;;66:873-876.
Lal S, Allen J, Etienne P, et al:  Dopaminergic function in Gilles de la Tourette's syndrome, Sydenham's chorea and torsion dystonia . Clin Neurol Neurosurg 1976;;79:66-69.
Tabaddor K, Wolfson LI, Sharpless NS:  Diminished ventricular fluid dopamine metabolites in adult-onset dystonia . Neurology 1978;;28:1254-1258.
Wolfson LI, Sharpless NS, Thal LJ, et al:  Decreased ventricular fluid norepinephrine metabolite in childhood-onset dystonia . Neurology 1983;;33:369-372.

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