British Journal of Neurosurgety ( 1990) 4, 123- 126
ORIGINAL ARTICLE
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 02/02/15 For personal use only.
Electrolyte concentrations in serum and CSF following subarachnoid haemorrhage H. VON HOLST & T. MATHIESEN
Department of Neurosurgery, Karolinska Hospital, S-105 21 Stockholm, Sweden
Abstract Serum and CSF calcium, magnesium, potassium and sodium were analyzed in 14 patients suffering from subarachnoid haemorrhage and in 10 healthy controls. The calcium and potassium concentrations in serum and CSF were decreased while magnesium unchanged and sodium were unchanged. A deranged electrolyte homeostasis was thus detectable in the CSF following subarachnoid haemorrhage. It could not be established whether symptoms of delayed cerebral ischemia were related to CSF calcium and/or potassium levels.
Key words: Subarachnoid haemorrhage, electrolytes, cerebrospinal fluid.
Introduction The serum and cerebrospinal fluid (CSF) concentrations of calcium, magnesium, sodium and potassium have been well described in healthy persons and in patients suffering from brain tumours or hydrocephalus'. A stable extracellular milieu is necessary for neuronal conduction in the CNS. It appears that the CSF concentrations of these ions are regulated by processes other than passive diffusion over the blood brain barrier (BBB)Z-5. Normally, the CSF concentrations of calcium and potassium are lower than in serum while sodium and magnesium are higher6-7. In patients with hydr~cephalus~-~, the CSF concentrations of calcium, magnesium and sodium are increased while potassium is decreased. In patients with meningitis, the CSF concentration of magnesium are decreased and calcium increased'O. Similarly, the electrolyte gradients between the intra and extracellular spaces and the gradients over the BBB tend to disappear post-mortem". In experimental subarachnoid haemorrhage
(SAH), a momentary bleeding into the subarachnoid space is followed by an extracellular increase in potassium and a decrease in calciumI2. Calcium entry into cells has been regarded as an important step in ischemic cell death13-14 and in cerebral vasospasm after SAH". Treatment with the calcium blocking agent Nimodipine has improved the outcome of SAH by diminishing ischemic deficitsl6-I7. In this report, the serum and CSF concentrations of calcium, magnesium, sodium and potassium were analyzed to characterize gross changes of serum and CSF electrolytes that accompany SAH and may influence its course.
Materials and methods Serum and CSF samples were obtained from 14 patients suffering from SAH and from 10 neurologically healthy persons. Samples from the SAH patients were drawn at days 3,6 and 9 after haemorrhage. In addition, seven 10 ml portions of CSF were obtained via a lumbar
123
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 02/02/15 For personal use only.
124
H. von Holst 13T. Mathiesen
drain at surgery on days 9-12 from 13 patients operated for an intracranial aneurysm 10-15 days after SAH. All samples were immediately spun down and the supernatants were stored at -20°C until analysis. The CSF protein content was (0.5 g/l in all subjects. Sodium, potassium, calcium and magnesium were analyzed by an Ektachem 700 automatic analyzer (Kodak, Rochester, NY). Statistical analysis included the MannWhitney U-test for comparisons between groups and the paired Student's t-test for comparisons between samples obtained at different time points from the same patients. Calculations were performed with Statview software on a MacintoshPlus personal computer.
the serum and CSF levels were not significantly altered following SAH (serum 1 4 1 . 3 f 2 . 0 ~141.5f13.2;CSF ~ 135.7k0.7~~ 132.6 k 5.9). Figure 2 shows the mean concentrations of electrolytes in different portions of CSF. The first samples reflect lumbar CSF while samples 6-7 represent central CSF (von Holst, 1985). The calcium concentration were lower in the last samples ( ~ ( 0 . 0 2 5 , Student's t-test) while magnesium, sodium and potassium remained relatively unchanged. Discussion
The serum and CSF electrolyte levels of our controls were comparable to normal values reported by previous investigators1*I8. The mean values of serum sodium and potassium were lower than expected but the small size of Results the group could well account for the finding. A Figure 1 shows the mean electrolyte concen- correction for protein contents was not made trations at days 3,6 and 9 for the 14 patients. A since ionized calcium is in equilibrium with significant calcium increase from day 3 to days protein bound calcium and thus the total 6 and 9 was detected in CSF (~(0.025; calcium levels reflect the biologically available Student's t-test) but not in serum (p>0.3) of calcium in the body fluidsIg. patients suffering from SAH. For magnesium, In SAH patients, the haemorrhage per se significant changes of CSF levels were not allows serum products to enter the CSF detected while a decrease of serum magnesium without passing the BBB. After the bleeding decrease was noted (ptO.01). Significant episode, further damage to the BBB does not changes of CSF or serum sodium levels were seem to occur. The normal CSF protein levels not found. Potassium levels decreased in the of our patients would also be compatible with CSF (pt0.025) but did not change signifi- an intact BBB function. Still, marked changes cantly in serum. in electrolyte levels were detectable. The A statistical comparison of the mean serum serum and CSF calcium, the serum magnesium and CSF concentrations of calcium, magne- and the CSF potassium concentrations were sium, potassium and sodium was made be- decreased after SAH. The findings in SAH are tween controls and the study group. Serum and thus different from those in patients suffering CSF calcium were significantly lower at day 3 from hydrocephalus or meningiti~'.~. Previous in SAH patients (pt0.001, Mann-Whitney authors' have explained electrolyte changes in U-test) than in controls (serum 2.48 f0.09 vs meningitis as by BBB damage. BBB damage 1.95k0.44; CSF 1.32f0.37 vs 1.01f0.15). does not seem to explain the changes detected The magnesium concentrations were not signi- in these patients. This was also shown in a ficantly different in SAH patients and controls previous study where damage to the BBB could (serum 0.88k0.09 vs 0.87k0.38; CSF not be detected in SAH patients*O. Hub1.16f0.05 vs 1.14f0.10). The CSF potas- schmann et a1.I2reported a parallel increase in sium levels were decreased in SAH patients extracellular potassium and decrease in extra(pt0.005), while serum levels were not cellular calcium after experimental SAH. The (serum 3.88f0.25 vs 3.70k0.76; CSF potassium increase was, however, of short 2.90 f0.10 vs 2.42 k 0.52). Regarding sodium, duration and does not necessarily contradict
Electrolytes in SAH
125
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Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 02/02/15 For personal use only.
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0 FIG. 1. (1-4) Serum and CSF levels (Mean+SD) of calcium, magnesium, sodium and potassium at different time points following aneurysmal subarachnoid haemorrhage.
FIG. 2. (1-4) Serum and CSF levels in different CSF fractions representation a gradient from peripheral to central CSF in patients 7-1 1 days following aneurysmal subarachnoid haemorrhage.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 02/02/15 For personal use only.
126
H. von Holst 0 T. Mathiesen
our findings of low potassium levels in the CSF. The potassium decrease detectable in the later phase (3-9 days) after SAH, may be caused by an alteration of the active transport systems or by an increase of potassium reabsorption from the CSF. The calcium decrease may reflect its transport into cells in a cascade of ischemic injury. A correlation between symptoms of delayed cerebral ischemia and calcium concentrations was not detectable. The number of patients studied was, however, small and a possible relationship of ischemic symptoms and calcium levels needs further study. Contrary to the protein concentration, which increases 1.6 fold from central CSF to lumbar CSF, the electrolytes remained stable. The only exception was a decrease of calcium concentration in central CSF, probably reflecting the lower protein content of central CSF. This calcium gradient was expected since calcium is protein bound to a high degree. The finding agrees with the lower level of calcium in the ventricles than in lumbar CSF of normal rabbits'. A disturbance in CSF hypoxanthine, monoamine metabolites, amino acids and somatomedins2' has been shown for SAH patients. The present study indicates that the delicate electrolyte balance of the CSF or brain tissue also shows a derangement following SAH.
Address for correspondence: T. Mathiesen, Department of Neurosurgery, Karolinska Hospital, S-10521 Stockholm, Sweden. References Davson H. Physiology of the Cerebrospinal Fluid. London: Churchill, 1977. Fenstermacher JD, Rall DP. Physiology and pharmacology of cerebrospinal Fluid. In: Capri A. ed. Pharmacology of the Cerebral Circulation. New York: Pergamon Press, 1972; 41-72. Ames A 111, Higashi K, Nesbett FB. Relation of potassium concentration in choroid plexus fluid to that in plasma. J Physiol (London) 1965; 181:506-15.
Bradbury MWB, Davson H. The transport of potassium between blood, cerebrospinal fluid and brain. J Physiol (London) 1965; 181:151-74. Bradbury MWB, Kleeman CR. Stability of the potassium content of cerebrospinal fluid and brain. Am J Physiol 1967; 213519-28. Flexner LB. Changes in the chemistry and nature of the cerebrospinal fluid during fetal life in the pig. Am J Physiol 1938; 124:131-5. Milhorat TH. Modern concepts of hydrocephalus. Acta Neurol Lat Am (Suppl. 1) 1971; 17:195-205. Nagy G, Molnar L, Kovacs T, Nyako G, Rochlitz S. Elektrolytgehalt des liquor cerebrospinalis bei hydrocephalus. Arch Psychiair Nervenkr 1979; 226:3 19-24. 9 Cerda M. Manterola A. Ponce S. Basauri L. Electrolyte levels in' the CSF of children with non-tumoral hydrocephalus. Child's Nerv Syst 1985; 1:306-11. 10 Nauman HN. Cerebrospinal fluid electrolytes after death. Proc SOCexp Biol NY 1958; 98:16-18. 11 Hunter G, Smith HV. Calcium and magnesium in human cerebrospinal fluid. Nature (London) 1960; 186:161-2. 12 Hubschmann OR, Nathanson DC. Calcium and membrane dysfyunction in trauma and CSF. J Neurosurg 1985; 62:697-703. 13 Schanne FAX, Kane AB, Young EE. Calcium dependence of toxic cell death: a final common pathway. Science 1979; 206:700-2. 14 Siesjo BK. Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1981; 1:155-85. 15 Allen GS, Gross CJ, Henderson LM. Cerebral arterial spasm. Part 4: In vitro effects of temperature, serotonin analogues, large non-physiological concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery. J Neurosurg 1976; 44585-93. 16 Auer LM. Acute surgery of cerebral aneurysms and prevention of symptomatic vasospasm. Acta Neurochirurgica 1983; 69:272-81. 17 Ljunggren B, Brandt L, Saveland H, Nilsson PE, Cronqvist S, Anderson KE, Vinge E. Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 1984; 61:864-73. 18 Rapoport SI. The Blood-brain Barrier in Physiology and Medicine. New York: Raven Press, 1975. 19 Laurel1 CB, Lundh B, Nosslin B. Klinisk keini i praktisk medicin. Studentlitteratur Lund 1979; 93. 20 von Holst H,Ericsson K, Edner G. Positrom emission tomography with 68-Ga-EDTA and computed tomography in patients with subarachnoid Haemorrhage. Acta Neurochirurgica 1989; 97:146-9. 21 von Holst H. Adenine nucleotide and monoaminr metabolites, amino acids and somatomedins in human cerebrospinal fluid after subarachnoid haemorrhage. Thesis. [ISBN 91-7222-881-41 Stockholm: Karolinska Institute, 1985.
ORIGINAL ARTICLE
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 02/02/15 For personal use only.
Electrolyte concentrations in serum and CSF following subarachnoid haemorrhage H. VON HOLST & T. MATHIESEN
Department of Neurosurgery, Karolinska Hospital, S-105 21 Stockholm, Sweden
Abstract Serum and CSF calcium, magnesium, potassium and sodium were analyzed in 14 patients suffering from subarachnoid haemorrhage and in 10 healthy controls. The calcium and potassium concentrations in serum and CSF were decreased while magnesium unchanged and sodium were unchanged. A deranged electrolyte homeostasis was thus detectable in the CSF following subarachnoid haemorrhage. It could not be established whether symptoms of delayed cerebral ischemia were related to CSF calcium and/or potassium levels.
Key words: Subarachnoid haemorrhage, electrolytes, cerebrospinal fluid.
Introduction The serum and cerebrospinal fluid (CSF) concentrations of calcium, magnesium, sodium and potassium have been well described in healthy persons and in patients suffering from brain tumours or hydrocephalus'. A stable extracellular milieu is necessary for neuronal conduction in the CNS. It appears that the CSF concentrations of these ions are regulated by processes other than passive diffusion over the blood brain barrier (BBB)Z-5. Normally, the CSF concentrations of calcium and potassium are lower than in serum while sodium and magnesium are higher6-7. In patients with hydr~cephalus~-~, the CSF concentrations of calcium, magnesium and sodium are increased while potassium is decreased. In patients with meningitis, the CSF concentration of magnesium are decreased and calcium increased'O. Similarly, the electrolyte gradients between the intra and extracellular spaces and the gradients over the BBB tend to disappear post-mortem". In experimental subarachnoid haemorrhage
(SAH), a momentary bleeding into the subarachnoid space is followed by an extracellular increase in potassium and a decrease in calciumI2. Calcium entry into cells has been regarded as an important step in ischemic cell death13-14 and in cerebral vasospasm after SAH". Treatment with the calcium blocking agent Nimodipine has improved the outcome of SAH by diminishing ischemic deficitsl6-I7. In this report, the serum and CSF concentrations of calcium, magnesium, sodium and potassium were analyzed to characterize gross changes of serum and CSF electrolytes that accompany SAH and may influence its course.
Materials and methods Serum and CSF samples were obtained from 14 patients suffering from SAH and from 10 neurologically healthy persons. Samples from the SAH patients were drawn at days 3,6 and 9 after haemorrhage. In addition, seven 10 ml portions of CSF were obtained via a lumbar
123
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 02/02/15 For personal use only.
124
H. von Holst 13T. Mathiesen
drain at surgery on days 9-12 from 13 patients operated for an intracranial aneurysm 10-15 days after SAH. All samples were immediately spun down and the supernatants were stored at -20°C until analysis. The CSF protein content was (0.5 g/l in all subjects. Sodium, potassium, calcium and magnesium were analyzed by an Ektachem 700 automatic analyzer (Kodak, Rochester, NY). Statistical analysis included the MannWhitney U-test for comparisons between groups and the paired Student's t-test for comparisons between samples obtained at different time points from the same patients. Calculations were performed with Statview software on a MacintoshPlus personal computer.
the serum and CSF levels were not significantly altered following SAH (serum 1 4 1 . 3 f 2 . 0 ~141.5f13.2;CSF ~ 135.7k0.7~~ 132.6 k 5.9). Figure 2 shows the mean concentrations of electrolytes in different portions of CSF. The first samples reflect lumbar CSF while samples 6-7 represent central CSF (von Holst, 1985). The calcium concentration were lower in the last samples ( ~ ( 0 . 0 2 5 , Student's t-test) while magnesium, sodium and potassium remained relatively unchanged. Discussion
The serum and CSF electrolyte levels of our controls were comparable to normal values reported by previous investigators1*I8. The mean values of serum sodium and potassium were lower than expected but the small size of Results the group could well account for the finding. A Figure 1 shows the mean electrolyte concen- correction for protein contents was not made trations at days 3,6 and 9 for the 14 patients. A since ionized calcium is in equilibrium with significant calcium increase from day 3 to days protein bound calcium and thus the total 6 and 9 was detected in CSF (~(0.025; calcium levels reflect the biologically available Student's t-test) but not in serum (p>0.3) of calcium in the body fluidsIg. patients suffering from SAH. For magnesium, In SAH patients, the haemorrhage per se significant changes of CSF levels were not allows serum products to enter the CSF detected while a decrease of serum magnesium without passing the BBB. After the bleeding decrease was noted (ptO.01). Significant episode, further damage to the BBB does not changes of CSF or serum sodium levels were seem to occur. The normal CSF protein levels not found. Potassium levels decreased in the of our patients would also be compatible with CSF (pt0.025) but did not change signifi- an intact BBB function. Still, marked changes cantly in serum. in electrolyte levels were detectable. The A statistical comparison of the mean serum serum and CSF calcium, the serum magnesium and CSF concentrations of calcium, magne- and the CSF potassium concentrations were sium, potassium and sodium was made be- decreased after SAH. The findings in SAH are tween controls and the study group. Serum and thus different from those in patients suffering CSF calcium were significantly lower at day 3 from hydrocephalus or meningiti~'.~. Previous in SAH patients (pt0.001, Mann-Whitney authors' have explained electrolyte changes in U-test) than in controls (serum 2.48 f0.09 vs meningitis as by BBB damage. BBB damage 1.95k0.44; CSF 1.32f0.37 vs 1.01f0.15). does not seem to explain the changes detected The magnesium concentrations were not signi- in these patients. This was also shown in a ficantly different in SAH patients and controls previous study where damage to the BBB could (serum 0.88k0.09 vs 0.87k0.38; CSF not be detected in SAH patients*O. Hub1.16f0.05 vs 1.14f0.10). The CSF potas- schmann et a1.I2reported a parallel increase in sium levels were decreased in SAH patients extracellular potassium and decrease in extra(pt0.005), while serum levels were not cellular calcium after experimental SAH. The (serum 3.88f0.25 vs 3.70k0.76; CSF potassium increase was, however, of short 2.90 f0.10 vs 2.42 k 0.52). Regarding sodium, duration and does not necessarily contradict
Electrolytes in SAH
125
3.5
L
1.o .5
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 02/02/15 For personal use only.
0
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5
6
7
,
,
,
,
,
,
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3 4 Fraction
5
6
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(d)
0
0 FIG. 1. (1-4) Serum and CSF levels (Mean+SD) of calcium, magnesium, sodium and potassium at different time points following aneurysmal subarachnoid haemorrhage.
FIG. 2. (1-4) Serum and CSF levels in different CSF fractions representation a gradient from peripheral to central CSF in patients 7-1 1 days following aneurysmal subarachnoid haemorrhage.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 02/02/15 For personal use only.
126
H. von Holst 0 T. Mathiesen
our findings of low potassium levels in the CSF. The potassium decrease detectable in the later phase (3-9 days) after SAH, may be caused by an alteration of the active transport systems or by an increase of potassium reabsorption from the CSF. The calcium decrease may reflect its transport into cells in a cascade of ischemic injury. A correlation between symptoms of delayed cerebral ischemia and calcium concentrations was not detectable. The number of patients studied was, however, small and a possible relationship of ischemic symptoms and calcium levels needs further study. Contrary to the protein concentration, which increases 1.6 fold from central CSF to lumbar CSF, the electrolytes remained stable. The only exception was a decrease of calcium concentration in central CSF, probably reflecting the lower protein content of central CSF. This calcium gradient was expected since calcium is protein bound to a high degree. The finding agrees with the lower level of calcium in the ventricles than in lumbar CSF of normal rabbits'. A disturbance in CSF hypoxanthine, monoamine metabolites, amino acids and somatomedins2' has been shown for SAH patients. The present study indicates that the delicate electrolyte balance of the CSF or brain tissue also shows a derangement following SAH.
Address for correspondence: T. Mathiesen, Department of Neurosurgery, Karolinska Hospital, S-10521 Stockholm, Sweden. References Davson H. Physiology of the Cerebrospinal Fluid. London: Churchill, 1977. Fenstermacher JD, Rall DP. Physiology and pharmacology of cerebrospinal Fluid. In: Capri A. ed. Pharmacology of the Cerebral Circulation. New York: Pergamon Press, 1972; 41-72. Ames A 111, Higashi K, Nesbett FB. Relation of potassium concentration in choroid plexus fluid to that in plasma. J Physiol (London) 1965; 181:506-15.
Bradbury MWB, Davson H. The transport of potassium between blood, cerebrospinal fluid and brain. J Physiol (London) 1965; 181:151-74. Bradbury MWB, Kleeman CR. Stability of the potassium content of cerebrospinal fluid and brain. Am J Physiol 1967; 213519-28. Flexner LB. Changes in the chemistry and nature of the cerebrospinal fluid during fetal life in the pig. Am J Physiol 1938; 124:131-5. Milhorat TH. Modern concepts of hydrocephalus. Acta Neurol Lat Am (Suppl. 1) 1971; 17:195-205. Nagy G, Molnar L, Kovacs T, Nyako G, Rochlitz S. Elektrolytgehalt des liquor cerebrospinalis bei hydrocephalus. Arch Psychiair Nervenkr 1979; 226:3 19-24. 9 Cerda M. Manterola A. Ponce S. Basauri L. Electrolyte levels in' the CSF of children with non-tumoral hydrocephalus. Child's Nerv Syst 1985; 1:306-11. 10 Nauman HN. Cerebrospinal fluid electrolytes after death. Proc SOCexp Biol NY 1958; 98:16-18. 11 Hunter G, Smith HV. Calcium and magnesium in human cerebrospinal fluid. Nature (London) 1960; 186:161-2. 12 Hubschmann OR, Nathanson DC. Calcium and membrane dysfyunction in trauma and CSF. J Neurosurg 1985; 62:697-703. 13 Schanne FAX, Kane AB, Young EE. Calcium dependence of toxic cell death: a final common pathway. Science 1979; 206:700-2. 14 Siesjo BK. Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1981; 1:155-85. 15 Allen GS, Gross CJ, Henderson LM. Cerebral arterial spasm. Part 4: In vitro effects of temperature, serotonin analogues, large non-physiological concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery. J Neurosurg 1976; 44585-93. 16 Auer LM. Acute surgery of cerebral aneurysms and prevention of symptomatic vasospasm. Acta Neurochirurgica 1983; 69:272-81. 17 Ljunggren B, Brandt L, Saveland H, Nilsson PE, Cronqvist S, Anderson KE, Vinge E. Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 1984; 61:864-73. 18 Rapoport SI. The Blood-brain Barrier in Physiology and Medicine. New York: Raven Press, 1975. 19 Laurel1 CB, Lundh B, Nosslin B. Klinisk keini i praktisk medicin. Studentlitteratur Lund 1979; 93. 20 von Holst H,Ericsson K, Edner G. Positrom emission tomography with 68-Ga-EDTA and computed tomography in patients with subarachnoid Haemorrhage. Acta Neurochirurgica 1989; 97:146-9. 21 von Holst H. Adenine nucleotide and monoaminr metabolites, amino acids and somatomedins in human cerebrospinal fluid after subarachnoid haemorrhage. Thesis. [ISBN 91-7222-881-41 Stockholm: Karolinska Institute, 1985.
