Acta Neurol. Scandinav. 52, 137-144, 1975
Departments of Neurology and Pharmacology, University of Giiteborg, Goteborg, Sweden.
CONCENTRATIONS O F MONOAMINE METABOLITES IN HUMAN LUMBAR AND CISTERNAL CEREBROSPINAL FLUID
BARBRO JOHANSSON & BJORN-ERIK Roos ABSTRACT 5HIAA and HVA were determined in successive samples of CSF withdrawn a t the lumbar and cisternal levels in connection with gas myelographic examinations i n 16 patients. The mean of 5-IIIAA in the first eisternal samples were 83 ng/ml (n = 8) and of HVA 143 ng/ml ( n = 7 ) . A sharp increase i n the concentration of both metabolites, but particularly of HVA, was seen in successive lumbar samples. The ratio of cisternal/lumbar 5-HIAA was 3/1, and of HVA 10/1 in one patient i n whom Iumbar and cisternal CSF were obtained with 2 weeks’ interval. The concentrations of monoamine metabolites i n CSF obtained a t lumbar puncture are thus highly dependent on the amount of fluid withdrawn. This fact should be taken into consideration when different materials are compared.
Homovanillic acid (HVA), the main metabolite of dopamine, and 5-hydroxyindoleacetic acid ( 5-HIAA), the metabolite of 5-hydroxytryptamine (5-HT), have been investigated in the lumbar cerebrospinal fluid (CSF) in a number of clinical conditions and in normal subjects (for a recent review of the literature, see Johansson & Roos 1974). I1 is known that the concentrations of these metabolites are higher in ventricular fluid than in lumbar fluid, although different ventricular/ lumbar ratios have been suggested. Thus, Moir et al. (1970) reported 5.5/1 and 9/1 for 5-HIAA and HVA respectively, while Gordon (quoted by Tamarkin et al. 1970) found corresponding ratios to be 2/1 and 6/1. Much less is known about the nionoamine metabolite concentration in cisternal fluid in man. Moir e t al. (1970) and Garelis & Sourkes (1973) have reported cisternal values of 5-HIAA and HVA from one single patient each. They found 5-HIAA to be 85 and 86 ng/ml and HVA 185 and 188 ng/ml respectively, i.e. higher than in lumbar fluid, but lower than in ventricular fluid. By contrast, Bernheimer e t al. (1966) claimed that no difference between cisternal and lumbar
138
cerebrospinal fluid was obtained in their material. The aim of the present study was to determine the concentrations of HVA and 5-HIAA in successive portions of lumbar and cisternal fluid when large amounts of CSF were withdrawn in connection with the performance of gasmyelograms. MATERIAL AND METHODS
CSF was obtained in connectian with 19 gasmyelographic examinations, made according to Lindgren (1952) and Feria & Radberg (1967), in 16 patients. In three patients, the examinations were performed via both lumbar and cisternal routes; i n eight via the lumbar; and i n five via t h e cisternal route only. Ages varied from 30 to 64 years, apart from three patients who were 8, 10 and 82 years old. The diagnoses are given i n connection with the results. Lumbar and cisternal fluid were collected w i t h t h e patient i n t h e lateral recumbent position. During cisternal (suboccipital) puncture the examination table was tilted, with the head of t h e patient 15-20 degrees lower than the feet, and it remained i n this position until the fluid withdrawal was finished. When lumbar puncture was performed, t h e feet of the patients were 15-25 degrees lower than the head. The fluid was usually withdrawn before any gas was injected at the lumbar level, but i n a few patients 6-8 m l gas was injected initially to see if t h e gas could pass a block. At the cisternal level t h e injection of gas was usually started after approximately 30 m l fluid had been taken out (the same amount of gas as fluid removed), and then the fluid withdrawal and gas injection were alternated. The total amount of fluid was collected within 10 min. A l l t h e fluid sampling was supervised by one of us (BJ). Each of the successive lumbar samples contained 10 m l fluid, and each of the cisternal samples 6 ml. The analyses of HVA were done spectrophotofluorimetrically as described by Korf ef al. (1971) and 5-HIAA by the method of Ashcroff & Sharman (1960), with some modifications (Johansson & Roos 1974). Care was taken to avoid intake of salicylic acid f o r some days before the myelograms, as contamination with this drug interferes with t h e determination of HVA. However, this was not always possible and, i n a few cases, only 5-HIAA could be determined. The patients were premedicated with 100 mg phenobarbitol, and kept fasting from t h e evening prior to the investigation.
RESULTS
Of 11 patients from whom fluid was withdrawn at the lumbar level: five had no blocks on electromanometric recordings; two had a partial block, but no hindrance for the passage of gas; and four had a total or subtotal block. The means of 5-HIAA and of HVA in the initial 10 ml sample in the seven patients with no block or partial block were 30 ng/mI (27-41) and 2 4 ng/ml (13-46), respectively. If the two patients with partial block are omitted, 5-HIAA does not change and HVA would be 28 ng/ml. Figure 1 shows the concentration increase in successive 10 ml samples in four patients with no restriction of flow (I, 111, and I V ) , or with a slight block (11). In patient IV, an initial
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1 3 5 No. 1 3 5 N o Figure 1. A --- A 5-HIAA, o o H V A in successiue 10 ml lumbar samples. Arrow indicates gas injection. Cases: I. Severe scoliosis. N o neurological symptoms. Myelogram normal. I I . Dissociated sensibility disfurbance below T 7. Partial block (slight). Myelogram indicated d i f f u s e enlargement of the spinal cord in the upper thoracic region, but n o hindrance f o r passage of gas. S y m p t o m s regressed. A later myelogram normal, I I I . Bladder disturbanee. Myelogram normal. IV. Pain and sensibilitg disturbance at T 2 level. Myelogram normal but surgical exploration showed a small neurinoma o n T 2.
portion of fluid ( 6 ml) was taken for other investigations, which explains the rather high HVA concentration in the first sample. In one of the patients not represented in the figures ( a 57-year-old man with a slight myelopathy after a herpes zoster infection), only 5-HIAA was obtained. The initial value was 41 ng/ml, and in the 8th sample it had increased to 79 ng/ml. In another patient with a moderate degree of cervical myelopathy, no block and normal myelogram, 5-HIAA increased from 24 to 36 ng/ml and HVA from 15 to 63 ng/ml (30 ml withdrawn). Figure 2 shows the results from four patients with severely restricted
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1 3 5 No. I 3 No. Figure 2 . 5 - H I A A in !urnbar A - - - A and cisternal A-A f l u i d . H V A in o and cisternal 0-• f l u i d . Four p a t i e n f s w i t h spinal fumours lumbar o and severelu restricted f l o w . I , I I and I l l t o l d , I V subtotal block. In I and I I 6-8 m l gas w a s injecied before f l u i d withdrawal.
flow. Low HVA and rather high concentrations of 5-HIAA were found in the first two patients. I n 111 and IV, the myelographic examinations were started via the lumbar route and continued via the cisternal route the same day. Cisternal fluid: The means of 5-HIAA and of HVA in the first cisternal samples were 83 (56-136) ng/ml ( 8 patients) and 143 (90-207) ng/ml ( 7 patients), respectively. Figure 3 shows the concentration of the metabolites in successive samples in four of the patients. When gas was injected-as indicated by arrows-a lowering of the concentration occurred, indicating mixing with spinal fluid. In the 6th 10 ml sample withdrawn at the lumbar level in patient IV (Figure 3 ) , the concentrations of 5-HIAA and HVA were similar to those found in the first cisternal sample. The ratio between cisternal and lumbar concentration of 5-HIAA was 3/1 and of HVA 10/1 in this patient. The ratios between cisternal and spinal 5-HIAA in the two patients with block (111 and IV, Figure 2 ) were 2.4/1 and 4.7/1. The first cisternal sample from the only patient not represented in the figures contained 76 ng/ml 5-HIAA and 167 ng/ml HVA, and the last sample 73 and 139 ng/ml, respectively (42 ml was withdrawn).
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Figurr 3. 5-HIAA in l u m b a r A - - - A and cisternal A--A f l u i d . H V A in f l u i d . L u m b a r f l u i d : Successive 10 m f lumbar 0 - - - o and cisternal o-@ samples. Cisternal f l u i d : Successive 6 m l samples. Arrows indicate gas injection [ i n II: arrows refer t o cisternal fluid onlll). Cases: I . Spastic paraparesis. Myelogram showed a narrow spinal canal b u t no t u m o u r . II. S y m p t o m s indicating compression of t h e cervical spinal cord. Partial block. M{jelogram: a disc prolapse C IV-1’. I l l . Acute severe post-traumatic tetraparesis. Subtotal regress o f srimptoms within I week. N o block. Myelogram normal. I V . Slight post-traumatic tetraparesis. Partial block. L u m b a r and cisternal mgelograms [performed w i t h 2 weeks’ interval) indicated a cervical disc prolapse hui the gas could pass freely.
An earlier lumbar puncture had revealed a partial block, and the cisternal/lumbar ratio for 5-HIAA was 3/1. (No HVA was determined in the spinal fluid.) One myelographic examination via the cisternal route was performed with a different technique (Figure 4). After withdrawal of 12 ml fluid, 12 ml gas was injected, and then this procedure of withdrawal of this small amount of fluid followed by gas injection was repeated several times. This procedure did not result in the sharp
142
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113 115 117 119 121 123 t25 t27 N o
Figure 4 . 5 - H I A A in successive 6 m l cisternal samples in a m a n w i t h pain and progressive weakness o f the right leg. N o bloclc and no relevant findings in the mgelogram.
concentration decrease after gas injections seen with the regular technique, indicating a more gradual mixing of the different compartment s. DISCUSSION
The values of 5-HIAA and HVA varied much more in the first sample of fluid drawn at the lumbar lever than in the following samples. The concentration of 5-HIAA was generally double in the third or fourth sample. The increase of HVA was larger, e.g. ninefold in the 4th sample in one patient (No. I, Figure l ) , and tenfold in the 6th sample in another (No. IV, Figure 3 ) . 5-HIAA in spinal fluid derives from both brain and spinal cord, while HVA comes almost exclusively from the brain. The partial block in patient 11, Figure 1 and patient IV, Figure 3 might have some significance for the low initial HVA, although the CSF blocks registered electromanometrically were slight (method see Gilland 1966) and other patients with no block had similarly low values. We have earlier found normal HVA concentration in patients with partial block (Johansson & Roos 1974). The low values of HVA in patients with severe spinal block (Figure 2 ) are in agreement with the findings by Curzon et al. (1971), Garelis & Sourkes (1973) and Johansson & Roos ( 1974). Two patients with a complete block of short duration had high values of spinal 5-HIAA (Figure 2 ) . An explanation might be that the synthesis of 5-HT and formation of 5-HIAA continues intraneuronally for a few days (cf. Magnusson 1973), although the release of 5-HT
143 depending on a regular impulse flow disappears. As the clearance of 5-HIAA from the spinal fluid to the blood at the spinal level is probably low, 5-HIAA might temporarily accumulate locally due to the block. At a later stage, 5-HIAA is decreased in lumbar fluid in patients with complete spinal lesions (Johansson & Roos 1974). There is an active out-transport of 5-HIAA and HVA from the CSF in the region of the fourth ventricle (Ashcroft et al. 1968). Compared to reported values for 5-HIAA and HVA in ventricular fluid (Moir e f al. 1970, Papesrhi et al. 1970, W e s t et al. 1972), our results would indicate a cisternal/ventricular gradient of 1/2-3 for HVA ; while the concentration of 5-HIAA in cisternal fluid is within the same range as or only slightly lower than in ventricular fluid. (We have a small 1111published ventricular material that suggests somewhat higher 5-HIAA values.) Part of the 5-HIAA in the cisternal fluid is probably produced in the brain stem, where a large amount of 5-HT containing neurons are present, and the concentration of the acid in the 4th ventricle might be considerably higher than in the lateral ventricles. Thus, even if there is an out-transport of 5-HIAA in the 4th ventricle, a considerable amount of the acid might reach the cisternal compartment. The rapid increase in concentration of the metabolites in successive lumbar samples makes it questionable i f the first ml withdrawn are representative of the conditions in the brain. Thus HVA concentrations in the first samples of the lumbar fluid in the patients represented in Figure 1 were 16, 18, 34 and 46 ng/ml, compared to 59, 49, 52 and 54 ng/ml in the second samples. In another patient with no block, the corresponding values were 15 and 56 ng/ml. It is obviously important that the amount of cerebrospinal fluid withdrawn should be mentioned in reports about monoamine metabolites in the cerebrospinal fluid. Great caution has to be taken when different materials are compared. Most of the CSF samples analysed by Bernheimer et al. ( 1966) were obtained by suboccipital puncture which might explain the high values of HVA in a number of their nonparkinsonian “control” patients (60 ng/ml). Likewise, the high value of HVA (100 ng/ml) reported by AndPn et al. (1963) was determined in a total amount of 50 ml fluid withdrawn in connection with lumbar gas myelographic examinations.
ACKNOWLEDGEMENTS This work was supported by the Swedish Medical Research Council (B73-21X-165-
09A). We thank Xlrs Ylva Johnsson and Miss Anna-Carin Brorson for skilful technical assistance, and Miss Ingrid Carlsson f o r careful preparation of the manuscript.
144 REFERENCES
Andda, N.-E., B. E. Roos
& B. Werdinius (1963) : The occurrence of homovanillic acid in brain and cerebrospinal fluid and its determination by fluorimetric method. Life Sci. 2, 448-458. Asheroft, G. W., R. C. Dow & A. T. B. Moir (1968): The active transport of 5-hydroxyindol-3-ylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid from a recirculatory perfusion system of the cerebral ventricles of the unanaesthetized dog. J. PhsioI. (Lond.) 199, 397-425. Ashcroft, G. W. & D. F. Sharman (1960) : 5-Hydroxyindoles in human cerebrospinal fluids. Nature (Lond.) 186, 1050-1051. Bernheimer, H., W. Birkmayer & 0. Hornykiewicz (1966) : Homovanillinsaure im Liquor cerebrospinalis : Untersuchungen beim Parkinson-Syndrom und anderen Erkrankungen des ZNS. Wien. klin. Wschr. 78, 417-419. Curzon, G., E. J. W. Gumpert & D. M. Sharpe (1971): Amine metabolites i n the lumbar cerebrospinal fluid of humans with restricted flow of cerebrospinal fluid. Nature New Biology 231, 189-190. Feria, L. G. & C. RIdberg (1967) : Complete gas myelography via lumbar injection under pressure. Radiology 88, 917-923. Gilland, 0 . (1966): CSF dynamic diagnosis of spinal block. VII. Reliability of lumbal electromanometric. Acta neurol. scand. 42, Suppl. 21, 45-73. Garelis, E. & T. I,. Sourkes (1973) : Sites of origin i n the central nervous system of monoamine metabolites measured in human cerebrospinal fluid. J. Neurol. Neurosurg. Psychiat. 36, 625-629. Johansson, B. & B.-E. Roos (19744) : 5-Hydroxyindoleacetic acid and homovanillic acid i n cerebrospinal fluid of patients with neurological diseases. Europ. Neurol. 11, 37-45. Korf, J., B.-E. Roos & B. Werdenius (1971) : Fluorometric determination of homovanillic acid i n tissues using anion exchange separation and mixed solvent elution. Acta chem. scand. 25, 333-335. Lindgren, E. (1952) : Myelographie. Lehrbuch der Rontgendiagnostik, ed. Schinz, Baensch, Fried1 & Uehlinger, 5th ed., vol. 11, pp. 1501-1524. Thieme, Stuttgart. Magnusson, T. (1973) : Effect of chronic transection on dopamine, noradrenaline and 5-hydroxytryptamine in the r a t spinal cord. Arch. Pharmacol. 278, 13-22. Moir, A. T. G., G. W. Ashcroft, T. B. B. Crawford, D. Eccleston & H. C. Guldberg (1970) : Cerehral metabolites in cerebrospinal fluid as a biochemical approach to the brain. Brain 93, 357-368. Papeschi, R., P. Molina-Negro, T. L. Sourkes, J. Hardy & C. Bcrtrand (1970): Concentration of homovanillic acid i n the ventricular fluid of patients with Parkinson’s disease and other dyskinesias. NeuroIogy (Minneap.) 20, 991-995. Tamarkin, N. R., F. K. Goodwin & J. AxeIrod (1970) : Rapid elevation of biogenetic amine metabolites i n human CSF following probenecid. Life Sci. 9, part I, 1397-1408. West, K. A., I,. Edvinsson, K. C. Niclsen & B.-E. Roos (1972) : Concentration of acid monoaminc metabolites in ventricular CSF of patients with posterior fossa tumors. Intracranial Pressure, ed. Brock 6: Diets, pp. 331-337. Springer Verlag. Berlin.
Received January 8, 1975.
Dr. Barbro Johansson Department of Neurology Sahlgren Hospital S-413 45 Goteborg, Sweden
Departments of Neurology and Pharmacology, University of Giiteborg, Goteborg, Sweden.
CONCENTRATIONS O F MONOAMINE METABOLITES IN HUMAN LUMBAR AND CISTERNAL CEREBROSPINAL FLUID
BARBRO JOHANSSON & BJORN-ERIK Roos ABSTRACT 5HIAA and HVA were determined in successive samples of CSF withdrawn a t the lumbar and cisternal levels in connection with gas myelographic examinations i n 16 patients. The mean of 5-IIIAA in the first eisternal samples were 83 ng/ml (n = 8) and of HVA 143 ng/ml ( n = 7 ) . A sharp increase i n the concentration of both metabolites, but particularly of HVA, was seen in successive lumbar samples. The ratio of cisternal/lumbar 5-HIAA was 3/1, and of HVA 10/1 in one patient i n whom Iumbar and cisternal CSF were obtained with 2 weeks’ interval. The concentrations of monoamine metabolites i n CSF obtained a t lumbar puncture are thus highly dependent on the amount of fluid withdrawn. This fact should be taken into consideration when different materials are compared.
Homovanillic acid (HVA), the main metabolite of dopamine, and 5-hydroxyindoleacetic acid ( 5-HIAA), the metabolite of 5-hydroxytryptamine (5-HT), have been investigated in the lumbar cerebrospinal fluid (CSF) in a number of clinical conditions and in normal subjects (for a recent review of the literature, see Johansson & Roos 1974). I1 is known that the concentrations of these metabolites are higher in ventricular fluid than in lumbar fluid, although different ventricular/ lumbar ratios have been suggested. Thus, Moir et al. (1970) reported 5.5/1 and 9/1 for 5-HIAA and HVA respectively, while Gordon (quoted by Tamarkin et al. 1970) found corresponding ratios to be 2/1 and 6/1. Much less is known about the nionoamine metabolite concentration in cisternal fluid in man. Moir e t al. (1970) and Garelis & Sourkes (1973) have reported cisternal values of 5-HIAA and HVA from one single patient each. They found 5-HIAA to be 85 and 86 ng/ml and HVA 185 and 188 ng/ml respectively, i.e. higher than in lumbar fluid, but lower than in ventricular fluid. By contrast, Bernheimer e t al. (1966) claimed that no difference between cisternal and lumbar
138
cerebrospinal fluid was obtained in their material. The aim of the present study was to determine the concentrations of HVA and 5-HIAA in successive portions of lumbar and cisternal fluid when large amounts of CSF were withdrawn in connection with the performance of gasmyelograms. MATERIAL AND METHODS
CSF was obtained in connectian with 19 gasmyelographic examinations, made according to Lindgren (1952) and Feria & Radberg (1967), in 16 patients. In three patients, the examinations were performed via both lumbar and cisternal routes; i n eight via the lumbar; and i n five via t h e cisternal route only. Ages varied from 30 to 64 years, apart from three patients who were 8, 10 and 82 years old. The diagnoses are given i n connection with the results. Lumbar and cisternal fluid were collected w i t h t h e patient i n t h e lateral recumbent position. During cisternal (suboccipital) puncture the examination table was tilted, with the head of t h e patient 15-20 degrees lower than the feet, and it remained i n this position until the fluid withdrawal was finished. When lumbar puncture was performed, t h e feet of the patients were 15-25 degrees lower than the head. The fluid was usually withdrawn before any gas was injected at the lumbar level, but i n a few patients 6-8 m l gas was injected initially to see if t h e gas could pass a block. At the cisternal level t h e injection of gas was usually started after approximately 30 m l fluid had been taken out (the same amount of gas as fluid removed), and then the fluid withdrawal and gas injection were alternated. The total amount of fluid was collected within 10 min. A l l t h e fluid sampling was supervised by one of us (BJ). Each of the successive lumbar samples contained 10 m l fluid, and each of the cisternal samples 6 ml. The analyses of HVA were done spectrophotofluorimetrically as described by Korf ef al. (1971) and 5-HIAA by the method of Ashcroff & Sharman (1960), with some modifications (Johansson & Roos 1974). Care was taken to avoid intake of salicylic acid f o r some days before the myelograms, as contamination with this drug interferes with t h e determination of HVA. However, this was not always possible and, i n a few cases, only 5-HIAA could be determined. The patients were premedicated with 100 mg phenobarbitol, and kept fasting from t h e evening prior to the investigation.
RESULTS
Of 11 patients from whom fluid was withdrawn at the lumbar level: five had no blocks on electromanometric recordings; two had a partial block, but no hindrance for the passage of gas; and four had a total or subtotal block. The means of 5-HIAA and of HVA in the initial 10 ml sample in the seven patients with no block or partial block were 30 ng/mI (27-41) and 2 4 ng/ml (13-46), respectively. If the two patients with partial block are omitted, 5-HIAA does not change and HVA would be 28 ng/ml. Figure 1 shows the concentration increase in successive 10 ml samples in four patients with no restriction of flow (I, 111, and I V ) , or with a slight block (11). In patient IV, an initial
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1 3 5 No. 1 3 5 N o Figure 1. A --- A 5-HIAA, o o H V A in successiue 10 ml lumbar samples. Arrow indicates gas injection. Cases: I. Severe scoliosis. N o neurological symptoms. Myelogram normal. I I . Dissociated sensibility disfurbance below T 7. Partial block (slight). Myelogram indicated d i f f u s e enlargement of the spinal cord in the upper thoracic region, but n o hindrance f o r passage of gas. S y m p t o m s regressed. A later myelogram normal, I I I . Bladder disturbanee. Myelogram normal. IV. Pain and sensibilitg disturbance at T 2 level. Myelogram normal but surgical exploration showed a small neurinoma o n T 2.
portion of fluid ( 6 ml) was taken for other investigations, which explains the rather high HVA concentration in the first sample. In one of the patients not represented in the figures ( a 57-year-old man with a slight myelopathy after a herpes zoster infection), only 5-HIAA was obtained. The initial value was 41 ng/ml, and in the 8th sample it had increased to 79 ng/ml. In another patient with a moderate degree of cervical myelopathy, no block and normal myelogram, 5-HIAA increased from 24 to 36 ng/ml and HVA from 15 to 63 ng/ml (30 ml withdrawn). Figure 2 shows the results from four patients with severely restricted
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1 3 5 No. I 3 No. Figure 2 . 5 - H I A A in !urnbar A - - - A and cisternal A-A f l u i d . H V A in o and cisternal 0-• f l u i d . Four p a t i e n f s w i t h spinal fumours lumbar o and severelu restricted f l o w . I , I I and I l l t o l d , I V subtotal block. In I and I I 6-8 m l gas w a s injecied before f l u i d withdrawal.
flow. Low HVA and rather high concentrations of 5-HIAA were found in the first two patients. I n 111 and IV, the myelographic examinations were started via the lumbar route and continued via the cisternal route the same day. Cisternal fluid: The means of 5-HIAA and of HVA in the first cisternal samples were 83 (56-136) ng/ml ( 8 patients) and 143 (90-207) ng/ml ( 7 patients), respectively. Figure 3 shows the concentration of the metabolites in successive samples in four of the patients. When gas was injected-as indicated by arrows-a lowering of the concentration occurred, indicating mixing with spinal fluid. In the 6th 10 ml sample withdrawn at the lumbar level in patient IV (Figure 3 ) , the concentrations of 5-HIAA and HVA were similar to those found in the first cisternal sample. The ratio between cisternal and lumbar concentration of 5-HIAA was 3/1 and of HVA 10/1 in this patient. The ratios between cisternal and spinal 5-HIAA in the two patients with block (111 and IV, Figure 2 ) were 2.4/1 and 4.7/1. The first cisternal sample from the only patient not represented in the figures contained 76 ng/ml 5-HIAA and 167 ng/ml HVA, and the last sample 73 and 139 ng/ml, respectively (42 ml was withdrawn).
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Figurr 3. 5-HIAA in l u m b a r A - - - A and cisternal A--A f l u i d . H V A in f l u i d . L u m b a r f l u i d : Successive 10 m f lumbar 0 - - - o and cisternal o-@ samples. Cisternal f l u i d : Successive 6 m l samples. Arrows indicate gas injection [ i n II: arrows refer t o cisternal fluid onlll). Cases: I . Spastic paraparesis. Myelogram showed a narrow spinal canal b u t no t u m o u r . II. S y m p t o m s indicating compression of t h e cervical spinal cord. Partial block. M{jelogram: a disc prolapse C IV-1’. I l l . Acute severe post-traumatic tetraparesis. Subtotal regress o f srimptoms within I week. N o block. Myelogram normal. I V . Slight post-traumatic tetraparesis. Partial block. L u m b a r and cisternal mgelograms [performed w i t h 2 weeks’ interval) indicated a cervical disc prolapse hui the gas could pass freely.
An earlier lumbar puncture had revealed a partial block, and the cisternal/lumbar ratio for 5-HIAA was 3/1. (No HVA was determined in the spinal fluid.) One myelographic examination via the cisternal route was performed with a different technique (Figure 4). After withdrawal of 12 ml fluid, 12 ml gas was injected, and then this procedure of withdrawal of this small amount of fluid followed by gas injection was repeated several times. This procedure did not result in the sharp
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113 115 117 119 121 123 t25 t27 N o
Figure 4 . 5 - H I A A in successive 6 m l cisternal samples in a m a n w i t h pain and progressive weakness o f the right leg. N o bloclc and no relevant findings in the mgelogram.
concentration decrease after gas injections seen with the regular technique, indicating a more gradual mixing of the different compartment s. DISCUSSION
The values of 5-HIAA and HVA varied much more in the first sample of fluid drawn at the lumbar lever than in the following samples. The concentration of 5-HIAA was generally double in the third or fourth sample. The increase of HVA was larger, e.g. ninefold in the 4th sample in one patient (No. I, Figure l ) , and tenfold in the 6th sample in another (No. IV, Figure 3 ) . 5-HIAA in spinal fluid derives from both brain and spinal cord, while HVA comes almost exclusively from the brain. The partial block in patient 11, Figure 1 and patient IV, Figure 3 might have some significance for the low initial HVA, although the CSF blocks registered electromanometrically were slight (method see Gilland 1966) and other patients with no block had similarly low values. We have earlier found normal HVA concentration in patients with partial block (Johansson & Roos 1974). The low values of HVA in patients with severe spinal block (Figure 2 ) are in agreement with the findings by Curzon et al. (1971), Garelis & Sourkes (1973) and Johansson & Roos ( 1974). Two patients with a complete block of short duration had high values of spinal 5-HIAA (Figure 2 ) . An explanation might be that the synthesis of 5-HT and formation of 5-HIAA continues intraneuronally for a few days (cf. Magnusson 1973), although the release of 5-HT
143 depending on a regular impulse flow disappears. As the clearance of 5-HIAA from the spinal fluid to the blood at the spinal level is probably low, 5-HIAA might temporarily accumulate locally due to the block. At a later stage, 5-HIAA is decreased in lumbar fluid in patients with complete spinal lesions (Johansson & Roos 1974). There is an active out-transport of 5-HIAA and HVA from the CSF in the region of the fourth ventricle (Ashcroft et al. 1968). Compared to reported values for 5-HIAA and HVA in ventricular fluid (Moir e f al. 1970, Papesrhi et al. 1970, W e s t et al. 1972), our results would indicate a cisternal/ventricular gradient of 1/2-3 for HVA ; while the concentration of 5-HIAA in cisternal fluid is within the same range as or only slightly lower than in ventricular fluid. (We have a small 1111published ventricular material that suggests somewhat higher 5-HIAA values.) Part of the 5-HIAA in the cisternal fluid is probably produced in the brain stem, where a large amount of 5-HT containing neurons are present, and the concentration of the acid in the 4th ventricle might be considerably higher than in the lateral ventricles. Thus, even if there is an out-transport of 5-HIAA in the 4th ventricle, a considerable amount of the acid might reach the cisternal compartment. The rapid increase in concentration of the metabolites in successive lumbar samples makes it questionable i f the first ml withdrawn are representative of the conditions in the brain. Thus HVA concentrations in the first samples of the lumbar fluid in the patients represented in Figure 1 were 16, 18, 34 and 46 ng/ml, compared to 59, 49, 52 and 54 ng/ml in the second samples. In another patient with no block, the corresponding values were 15 and 56 ng/ml. It is obviously important that the amount of cerebrospinal fluid withdrawn should be mentioned in reports about monoamine metabolites in the cerebrospinal fluid. Great caution has to be taken when different materials are compared. Most of the CSF samples analysed by Bernheimer et al. ( 1966) were obtained by suboccipital puncture which might explain the high values of HVA in a number of their nonparkinsonian “control” patients (60 ng/ml). Likewise, the high value of HVA (100 ng/ml) reported by AndPn et al. (1963) was determined in a total amount of 50 ml fluid withdrawn in connection with lumbar gas myelographic examinations.
ACKNOWLEDGEMENTS This work was supported by the Swedish Medical Research Council (B73-21X-165-
09A). We thank Xlrs Ylva Johnsson and Miss Anna-Carin Brorson for skilful technical assistance, and Miss Ingrid Carlsson f o r careful preparation of the manuscript.
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Received January 8, 1975.
Dr. Barbro Johansson Department of Neurology Sahlgren Hospital S-413 45 Goteborg, Sweden
