BIOL PSYCHIATRY 1990;27:891-896
891
Cencentration Gradients for HVA, 5-HIAA, Ascorbic Ac ,d, and Uric Acid in Cere ro pinal Fluid lstv~n Degr~:.~lland Erzs6bet Nagy
Concentratio:~s of HVA, .~~HIAA~ ~z:c~rbic acid, and uric acid in the lumbar and cisternal cerebrospinal fluid (CSF) were mtasured in psychiatric and. neurologically impaired patients. The concentration of HVA is 6.1 ~imes and of 5.HIAA 2.7 times higher in cisternal than in lumbar samples, the cisternaI level of uric acid iz half that of the lumbar region, but no significant differences were Jbund in ascorbic acid cotwentrations. Correlation between lumba., and cisternal met abolite concentrations is high for 5-HIAA and ascorbic ac~a', and is less for HVA wut uric acid. In c,sternal CSF there is a significant correlation between levels of HVA-5-HIAA, 5.HIAA-ascorbic acid, and 5-HIAA-uric acid. These correlations disappear in lumbar CSF. These findings indicate that extrapolations re,~cisternol ~eurotraasmitter metaboltw conce~tr~ion from lumbar measures are unwcrranted f ?r HVA, but not for 5-HIAA.
Introductivn The analysis of the dopamine and semtonin metabolite concentration ia lumbar cerebrospinal fluid (CSF) is the most widely used method for measuring the neurotransmitt~.r metabolism of the brain, it is hypothesized that neurotransmitter metabolite concentration of the CSF in the lateral ventricle could be an indicator of the rate of neurotransmitter metabolism (Papeschi et al. 1971, Sourkes 1973, Deg~ll et al. 1983, 1985). In freely moving cats, a marked, indivi¢~lally variable intraventricular concentration gradient w,:s found for Dopac, HVA, and 5.HIAA (Degrell et al. 1983). This makes the validity of the more caudall~ ~bta~ned CSF data less certain. A variety of factors make it difficult to find a direct relationship between ~he lumbar, cistemal, and ventrieular concentrations of neurotransmitter metabolites. Some of these include age. different sources of the metabolizes, the site and volu:~¢ of the CSF withdrawn, the motor activity and position of the patient, and the hour of ~e day (Gottfr~es e: al. 1969, Moir et al. 1970, Sourkes 1973, Garelis et al. 1974, Goodwin and Post 197.5, Bullet 1977, Post and Goodwin 1977, van Praag 1978, Wood 1980). One of the most important factors is the rostroca~dal concentration gradient for some
From the Department of Neurology and Psyc~i~T, University of Deb.~cen ~qedicalSchool, Debrecen, Hungary Address reprint requests to Dr. I. Degrell, Depart~ent of Neurology and Psychiatry, University of Debrecen Medical School, Nagyerdei krt. 98. ~I.4012 Debre~n, Hungat ;. Received March 23, 1988; ~,,~u~d June 10, 1989. Thb work was supported by t~e A. V. Humboldt Conmdttee. © 1990 S~iety of Biologicd Psychiatry
000~.3223/~!$03.$9
892
BIOL PSYCHL~,TRY 1990;27:891-89~
I. Degrell and E. Nagy
metabolites, par~icularly dopamine metabolites, homo~ anillic acid (HVA), dihydroxyphenylacetic acit~ (Do~ac), and 5-hydroxyindole acetic ~cid (5-HIAA), a serotonin metabolite. There is so~ne variability in ~ e reports on these concentration gradients. Siever et al. (1975) and Bertil~o:~ et ~. (1982) found a linear increase, but Jakupcevic et a~ (1977) found an exponential increase in concentrations of HVA and 5-HIAA in censecutive lumbar samples of CSF. For a better interpretation of the CSF data, concentration gradients were measured for HVA, 5-HIAA, uric acid, and ascorbic acid in lumbar and cisternal CSF.
Methods Eleven patients from our neurological and psychiatric departments received lumbar and cisternal punctures with the consent of the patients or their relatives. The protocol of the study was carried out in accordance with the Helsitfld declaration. Age, gender, and diagnosis of the patients are seen on the Table 1. Patients with a partial or total blockage of spinal CSF flow w~re excluded. Cistemal (4 ml) and lumbar (20 nd) CSF (the latter often immediately bciore pneamoencephalograpl~,y) were collected in an ice-cold glass t~be, divided, and immediately froze~ in liquid nitrogen. The samples were s~ored at - l~O°C in liquid nitrogen until ~alys~.~. The lumbar tap was performed after a cisternal puncture between the fourth and fifth lumbar vertebrae.
Results Lumbar (First 20 ml of CSF)--Cisternal Gradients Mean values, significant differences (one-tailed t-test), and correlation coefficients given in Table 2. The concentrations of HVA avd 5-HIAA were significantly h~gher, and uric acid was lowe,' in cisternal CSF. The concentraaon of HVA was 6.1 _ 2.7 times higher and the concentration of 5-HIAA was 2.7 _ 0.8 times higher in cisternal than in lum t ~ CSF. The concentration ~f uric ac~ in cisternal CSF wa~ 55% of the value ia lumbar CSF. There was a significant correlation between lumbar ant~ cisternal CSF for 5-HIAA and ascorbic acid; no significant correla~.ion was found for HVA and uric acid (p < 0.1 for both substances).
Correlation Between Metabolites in Cisternal and Lumbar CSF In cisternal CSF, HVA correlated significantly with 5-HIAA, and 5-HIAA with ascorbic acid and uric acid. HVA did not correlate with uric acid. In lumbar CSF, all the significant correlations mentioued in cisternal CSF disappeared (Table 3).
Discvssion The application of this information on neurotransmitter metabolite concentrations in CSF is greatly influenced by the inteq~tetation of these data. The concentrations of HVA and 5-HIAA are not homogeneous in ~e CSF because the local metabolite concentration of CSF reflects the neurotransmitte~" metabolism of the neighboring tissue. From the clinical (psyc~atdc) point of view, lumbar CSF is ~uspec'~; a lumbar sample of CSF can give only indirect information about the neurotransmitter metabolism of the brain.
CSF Gradients of H V A and 5-HIAA
BIOl. PSYCHIATRY 1990 27:891-896
893
Tattle 1. Age, Get~der, and Diagnosis of the Patients Patient
Gender
Age (years)
Diagnosis
1 2 3 4 5 6 7 8 9 i0 11
M M M M M M M M F M F
53 42 57 54 82 41 77 68 39 59 38
Chronic alcoholism, Korsako~Ts syndrowe Paranoid schizophrenia Chronic alcoholism, Korsakoffs syndrome Chronic alcoholism, KorsakoEs syndrome Senile demt. ~tia Chronic 2!ccho!ism, alcoholic dementia Multi-infarct dementia Mu|ti4nfarct dementia Hy~rtensive enceph~opathy Presenile dementia (Alzheimer's type) Huntington's chorea
Table 2. l,.~ean Values (ng/ml), Significant Diffe~r~ces, and Correlations o f HVA, 5-HIAA, Ascorbic as, J Uric Acid in Cisternal and Lumbar C £ F HVA mean153 SD ± 63 n il
Cistern~ CSF
mean 25.5 SD -- 10.3 n 11
Lumbar CSF Paired t-test Ratio ef cist./lumb. value,~ Correlatton Coefficient
Ascorbic acid
5-HIAA
Uric acid
49.5 ± 16.5 11
3069 ±2265 11
2274 ±714 9
18.2 "4-9.7 Ii
3118 ± 1815 11
4077 ± 1328 9
p < 0.001 6.1
891
Cencentration Gradients for HVA, 5-HIAA, Ascorbic Ac ,d, and Uric Acid in Cere ro pinal Fluid lstv~n Degr~:.~lland Erzs6bet Nagy
Concentratio:~s of HVA, .~~HIAA~ ~z:c~rbic acid, and uric acid in the lumbar and cisternal cerebrospinal fluid (CSF) were mtasured in psychiatric and. neurologically impaired patients. The concentration of HVA is 6.1 ~imes and of 5.HIAA 2.7 times higher in cisternal than in lumbar samples, the cisternaI level of uric acid iz half that of the lumbar region, but no significant differences were Jbund in ascorbic acid cotwentrations. Correlation between lumba., and cisternal met abolite concentrations is high for 5-HIAA and ascorbic ac~a', and is less for HVA wut uric acid. In c,sternal CSF there is a significant correlation between levels of HVA-5-HIAA, 5.HIAA-ascorbic acid, and 5-HIAA-uric acid. These correlations disappear in lumbar CSF. These findings indicate that extrapolations re,~cisternol ~eurotraasmitter metaboltw conce~tr~ion from lumbar measures are unwcrranted f ?r HVA, but not for 5-HIAA.
Introductivn The analysis of the dopamine and semtonin metabolite concentration ia lumbar cerebrospinal fluid (CSF) is the most widely used method for measuring the neurotransmitt~.r metabolism of the brain, it is hypothesized that neurotransmitter metabolite concentration of the CSF in the lateral ventricle could be an indicator of the rate of neurotransmitter metabolism (Papeschi et al. 1971, Sourkes 1973, Deg~ll et al. 1983, 1985). In freely moving cats, a marked, indivi¢~lally variable intraventricular concentration gradient w,:s found for Dopac, HVA, and 5.HIAA (Degrell et al. 1983). This makes the validity of the more caudall~ ~bta~ned CSF data less certain. A variety of factors make it difficult to find a direct relationship between ~he lumbar, cistemal, and ventrieular concentrations of neurotransmitter metabolites. Some of these include age. different sources of the metabolizes, the site and volu:~¢ of the CSF withdrawn, the motor activity and position of the patient, and the hour of ~e day (Gottfr~es e: al. 1969, Moir et al. 1970, Sourkes 1973, Garelis et al. 1974, Goodwin and Post 197.5, Bullet 1977, Post and Goodwin 1977, van Praag 1978, Wood 1980). One of the most important factors is the rostroca~dal concentration gradient for some
From the Department of Neurology and Psyc~i~T, University of Deb.~cen ~qedicalSchool, Debrecen, Hungary Address reprint requests to Dr. I. Degrell, Depart~ent of Neurology and Psychiatry, University of Debrecen Medical School, Nagyerdei krt. 98. ~I.4012 Debre~n, Hungat ;. Received March 23, 1988; ~,,~u~d June 10, 1989. Thb work was supported by t~e A. V. Humboldt Conmdttee. © 1990 S~iety of Biologicd Psychiatry
000~.3223/~!$03.$9
892
BIOL PSYCHL~,TRY 1990;27:891-89~
I. Degrell and E. Nagy
metabolites, par~icularly dopamine metabolites, homo~ anillic acid (HVA), dihydroxyphenylacetic acit~ (Do~ac), and 5-hydroxyindole acetic ~cid (5-HIAA), a serotonin metabolite. There is so~ne variability in ~ e reports on these concentration gradients. Siever et al. (1975) and Bertil~o:~ et ~. (1982) found a linear increase, but Jakupcevic et a~ (1977) found an exponential increase in concentrations of HVA and 5-HIAA in censecutive lumbar samples of CSF. For a better interpretation of the CSF data, concentration gradients were measured for HVA, 5-HIAA, uric acid, and ascorbic acid in lumbar and cisternal CSF.
Methods Eleven patients from our neurological and psychiatric departments received lumbar and cisternal punctures with the consent of the patients or their relatives. The protocol of the study was carried out in accordance with the Helsitfld declaration. Age, gender, and diagnosis of the patients are seen on the Table 1. Patients with a partial or total blockage of spinal CSF flow w~re excluded. Cistemal (4 ml) and lumbar (20 nd) CSF (the latter often immediately bciore pneamoencephalograpl~,y) were collected in an ice-cold glass t~be, divided, and immediately froze~ in liquid nitrogen. The samples were s~ored at - l~O°C in liquid nitrogen until ~alys~.~. The lumbar tap was performed after a cisternal puncture between the fourth and fifth lumbar vertebrae.
Results Lumbar (First 20 ml of CSF)--Cisternal Gradients Mean values, significant differences (one-tailed t-test), and correlation coefficients given in Table 2. The concentrations of HVA avd 5-HIAA were significantly h~gher, and uric acid was lowe,' in cisternal CSF. The concentraaon of HVA was 6.1 _ 2.7 times higher and the concentration of 5-HIAA was 2.7 _ 0.8 times higher in cisternal than in lum t ~ CSF. The concentration ~f uric ac~ in cisternal CSF wa~ 55% of the value ia lumbar CSF. There was a significant correlation between lumbar ant~ cisternal CSF for 5-HIAA and ascorbic acid; no significant correla~.ion was found for HVA and uric acid (p < 0.1 for both substances).
Correlation Between Metabolites in Cisternal and Lumbar CSF In cisternal CSF, HVA correlated significantly with 5-HIAA, and 5-HIAA with ascorbic acid and uric acid. HVA did not correlate with uric acid. In lumbar CSF, all the significant correlations mentioued in cisternal CSF disappeared (Table 3).
Discvssion The application of this information on neurotransmitter metabolite concentrations in CSF is greatly influenced by the inteq~tetation of these data. The concentrations of HVA and 5-HIAA are not homogeneous in ~e CSF because the local metabolite concentration of CSF reflects the neurotransmitte~" metabolism of the neighboring tissue. From the clinical (psyc~atdc) point of view, lumbar CSF is ~uspec'~; a lumbar sample of CSF can give only indirect information about the neurotransmitter metabolism of the brain.
CSF Gradients of H V A and 5-HIAA
BIOl. PSYCHIATRY 1990 27:891-896
893
Tattle 1. Age, Get~der, and Diagnosis of the Patients Patient
Gender
Age (years)
Diagnosis
1 2 3 4 5 6 7 8 9 i0 11
M M M M M M M M F M F
53 42 57 54 82 41 77 68 39 59 38
Chronic alcoholism, Korsako~Ts syndrowe Paranoid schizophrenia Chronic alcoholism, Korsakoffs syndrome Chronic alcoholism, KorsakoEs syndrome Senile demt. ~tia Chronic 2!ccho!ism, alcoholic dementia Multi-infarct dementia Mu|ti4nfarct dementia Hy~rtensive enceph~opathy Presenile dementia (Alzheimer's type) Huntington's chorea
Table 2. l,.~ean Values (ng/ml), Significant Diffe~r~ces, and Correlations o f HVA, 5-HIAA, Ascorbic as, J Uric Acid in Cisternal and Lumbar C £ F HVA mean153 SD ± 63 n il
Cistern~ CSF
mean 25.5 SD -- 10.3 n 11
Lumbar CSF Paired t-test Ratio ef cist./lumb. value,~ Correlatton Coefficient
Ascorbic acid
5-HIAA
Uric acid
49.5 ± 16.5 11
3069 ±2265 11
2274 ±714 9
18.2 "4-9.7 Ii
3118 ± 1815 11
4077 ± 1328 9
p < 0.001 6.1
