British Journal of Neurosurgery 1996;10(3):267±273 .... The latter included the insertions of 10 PS Medical Delta. à valves (PS Medical Corporation, Goleta, CA,.
B ritish Journal of N eurosurgery 1996;10(3):267± 273
O RIG INA L A RTIC LE
D oes the cerebrospinal ¯ uid protein concentration increase the risk of shunt complications? H. L. BRYDON 1 , R. HAYWARD 1 , W. HARK NESS 1 & R. BAYSTON 2 1
D epartment of N eurosurgery, Great Ormond Street H ospital for Children and 2 Departm ent of Academic M icrobiology, Institute of Child H ealth, London , U K.
A bstract A prospective study was performed to determine whether the popular opinion that a high C SF protein concentration increases the risk of shunt complications is true. Ninety-® ve patients were enrolled into the study and they had 116 shunt operations over 15 months. It was considered that the C SF protein content might in¯ uence the development of complications that occurred within 2 months of surgery. Shunt complications occurred following 24.6% of operations within this period. This included 12 infections, 13 obstructions and three cases of overdrainage. The distribution of complications, compared to CSF protein content, was non-signi® cant on a c 2 -test ( p . 0.5). The total protein content of each of the complication groups was also analysed using the M ann± Whitney U -test and the differences were nonsigni® cant for the infection (0.1 . p . 0.05) and obstruction groups (0.5 . p . 0.1). It is concluded that an elevated CSF protein content does not increase the risk of shunt com plications, and that there is no reason why shunting should be delayed in patients with a high CSF protein content. K ey w ords: H ydrocephalus, cerebrospinal ¯ uid shunts, cerebrospinal ¯ uid protein, shunt infectio n.
Introduction T here are few reports in the literature about the effects of an elevated CSF protein concentration upon shunt perform ance and complications. Furthermore, the few papers that have been published are case reports or short series, 1± 3 and describe only those patients who have developed com plications. T he incidence of shunt failure in hyperproteinorrhachic patients is therefore not known. Furtherm ore, it has not been determ ined whether an elevated protein content leads to an increased risk of shunt com plications, although this viewpoint is widely held by clinicians. The aim of this study w as to analyse CSF from patients undergoing shunt surgery, and correlate the results with subsequent com plications or the lack of them. However, a high C SF protein level will fall to norm al w ithin a few weeks and so only com plications occurring soon after surgery can be attributed to an abnorm al C SF com position. This interval has
not been de® ned in the literature, but has assum ed to be 8 weeks for this study. It is unusual for a high C SF protein concentration to persist beyond this period, but a shorter interval w ould have excluded several shunt infections, a com plication that has been attributed to a high CSF protein content.4 It is accepted that in m any cases the CSF w ill have returned to norm al within a shorter period. Our unit policy was not to shunt patients w ho were known to have a CSF protein of over 1.5 g/l. As the popular opinion is that an elevated C SF protein would increase the risk of shunt com plications, it w as not thought ethical to change this policy for the purposes of the study. H owever, m ost patients underwent surgery without a preoperative C SF analysis, and a num ber of them were later found to have a CSF protein content above this value. C om parison between groups of norm al and elevated CSF protein concentration w as therefore possible.
Correspondence to: Mr H. L. Brydon, Departm ent of Neurosurgery, Queen Elizabeth Hospital, Metchley Lane, Birm ingham B15 2TL, U K. Received for publication 13th June 1995 . Accepted 10th August 1995. 0268-869 7/96/030267 ± 07 $7.50 Ó
T he Neurosurgical Foundation
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T ABLE I. Aetiology of the hydrocephalus Diagnosis
Number
Intraventricular haem orrhage Tumour Idiopathic/congenital CNS malformation Postinfection Postsurgery/traum a Unknown Benign intracranial hypertension
27 24 17 15 7 3 3 1
Total
(28% ) (23% ) (18% ) (16% ) (7%) (3%) (3%) (1%) 95
P atients and m ethods Patients All patients undergoing shunt surgery during the 15 m onths from January 1992 to M arch 1993 were studied prospectively, provided that a peroperative specim en of CSF was obtained for analysis. Patients from whom a 2-m onth follow -up was not available w ere subsequently excluded from the study. The patient group consisted of 95 children, of w hom 56 underw ent their ® rst shunt insertion and 39 had an existing shunt revised. Overall, there were 52 boys and 43 girls (ratio 1.2:1). Their age range w as from 1 day to 14.9 years, but the age distribution was skewed, with 42% of them being less than 1 year old; the m edian age was 1.8 years and m ean 3.9 years. T he aetiology of the hydrocephalus is show n in T able I. M anagem ent T he 95 patients underwent 116 de® nitive shunt operations during the study period; i.e. operations that were not expected to result in the need for further surgery. The standard shunt used in G reat O rm ond Street Hospital for Children is the Cordis± H akim Ò system (Cordis UK , Brentford, Middlesex) and, because of its integral design, a complete replacem ent is often perform ed instead of a revision procedure. T hus, a com plete new shunt was inserted 90 tim es, the rem aining 26 operations being revisions of part of the shunt system only. T he latter included the insertions of 10 PS M edical D elta Ò valves (PS M edical Corporation, G oleta, C A, U SA), and one C odm an M edos Ò program m able valve, all for the m anagem ent of over-drainage sym ptom s. M ost shunts were placed into the peritoneum , but one existing ventriculoatrial shunt w as revised keeping the distal catheter within the atrium. In two cases biventricular system s were inserted for third ventricular tum ours. In 23 instances, shunts w ere inserted im m ediately following a period of external drainage or regular aspiration of a Rickham reservoir. T wo patients had tum our surgery perform ed at the sam e tim e as their
shunt was inserted, and one patient had a chronic subdural haem atom a drained during a shunt revision operation. At separate operations w ithin the same adm ission another four patients had tum ours excised and one had a stereotactic drainage of a craniopharyngiom a cyst. Prophylactic antibiotics were not given routinely, but were used in 19 instances, usually as continuation of treatm ent of a shunt infection, or w here other system ic conditions (e.g. im m unosuppression, skin rashes) were thought to increase the risk of shunt infection. However, sw abs soaked in povidone iodine were used to cover the wound edges during the operation, and a no-touch technique w as used throughout. Suspected shunt failure was investigated by C T and if the diagnosis was not clear, a shunt aspiration with m anom etric assessm ent of the intracranial pressure w as perform ed. Suspected overdrainage was investigated by 24-h intracranial pressure m onitoring before shunt revision. 5 Shunt infections were m anaged by shunt rem oval and external drainage in m ost cases, but an attem pt at im m ediately inserting a new shunt was m ade in one severely disabled patient.
C SF analysis T he CSF w as centrifuged at 2800 rev/m in (International Equipm ent Com pany, USA, M odel IEC C entra-7k) for 20 m in at 4 °C and bacteriological culture perform ed on the sedim ent. The total protein content of the supernatant was determ ined by a spectrophotom etric method using benzethonium chloride as the precipitating agent. 6 Individual protein fractions w ere m easured by agarose gel electrophoresis w ith nitrocellulose blotting 7 and staining using gold chloride. 8 T he electrophoresis strip was scanned using an Electrophoresis D ata Centre Scanner (H elena Laboratories, Texas, U SA), which gave the individual protein contents as a proportion of the total value. T he concentration of each individual protein in the C SF was calculated from the scan result and the C SF total protein content. The album in concentrations were m easured separately by electroim m unoassay, 9 using an agarose gel containing 0.5% goat anti-hum an album in antibodies (ATAB Atlantic Antibodies, Stillw ater, U SA). T his was because album in, being in a m uch higher concentration than the other proteins, m ight have saturated all of the adsorption sites on the nitrocellulose, and so have been incom pletely adsorbed. This would have resulted in an artefactually low result on the electrophoresis-scan m ethod. Statistical analysis was perform ed using the c 2 test, and the M ann± W hitney U-test on the SPSS Ò com puter program (SPSS Inc, C hicago, U SA).
Shunt complications and CSF proteins T ABLE II. Shunt com plications within 2 months of surgery
Complication
% of Number operations
Shunt infection Ventricular catheter obstruction Valve obstruction Peritoneal catheter obstruction Shunt disconnection Overdrainage
13 7 3 2 1 3
(9.8% ) (5.3% ) (2.3% ) (1.5% ) (0.8% ) (2.3% )
Total
29
(22.0% )
Results C om plications In total, 29 shunt-related com plications developed w ithin 8 weeks of surgery (Table II). There were no shunt com plication-related deaths, but one patient died from progression of his cerebral tumour 2 m onths after the shunt was inserted. C ontrol group T he control group consisted of patients that did not develop shunt complications and contained 91 C SF specim ens for analysis. The C SF total protein varied from 0.025 to 9.0 g/l, but 67% of them contained less than 0.5 g/l: the m edian value being 0.23 g/l. T here were 17 specim ens that contained over 1.0 g/l total protein. Each protein fraction was in a normal ratio to the total protein, 10 except for prealbumin, w hich was low. A breakdown of the CSF com position is given in T able III.
269
Shunt obstruction group T welve specim ens of CSF were obtained from patients who developed a shunt obstruction within the 2-m onth period: two peritoneal catheter obstructions, three valve obstructions and seven ventricular catheter obstructions. T he C T scans of this group of patients were review ed to assess the ventricular catheter positions and in no case did the catheter tip lie outside the ventricle. The total protein concentration varied from 0.1 to 12.3 g/l, but the latter specimen contained considerably m ore protein than the next highest (1.2 g/l), with all the others containing less than 1.0 g/l protein. The album in content of the 12.3 g/l specim en, as determ ined by electro-im m unoassay, was consistent with this result (i.e. 8.0 g/l, w hich was 65% of the total protein). However, the sam e patient had another C SF specim en taken at his next shunt revision 2 days later and the second specimen only contained 0.14 g/l total protein. It is m ost likely that the ® rst specim en had been contam inated by blood at the tim e of surgery, and this had elevated its protein content. However, that specim en had not been sent for cell counting and so there was no con® rm ation of this. The C SF com position of this group is shown in T able V . T he m ean and m edian total protein content of the group were higher than that of the controls, but the difference was not signi® cant (0.5 . p . 0.1). The concentration of m ost of the individual protein fractions did not differ signi® cantly between this and the control group (p . 0.5 for prealbum in and a -1 antitrypsin; 0.5 . p . 0.1 for album in, transferrin and tau-protein; and 0.1 . p . 0.05 for g -globu lin). However, haptoglobin had a higher mean and m edian value in this group (0.05 . p . 0.02).
Shunt infection group T en CSF specim ens were obtained from patients w ho subsequently developed shunt infections. Their total protein concentration varied from 0.2 to 2.4 g/l, but only one specim en contained m ore than 1.0 g/l. T he CSF com position is given in Table IV. The difference between the total protein content of this group and that of the controls w as not signi® cant on the M ann± W hitney U-test (0.1 . p . 0.05). F urtherm ore, the concentrations of m ost of the individual proteins did not differ signi® cantly from the control group (p . 0.5 for prealbum in; and 0.5 . p . 0.1 for album in, a -1 antitrypsin, haptoglobin and g -globulin). There was a signi® cant difference in the concentration of transferrin and tau-protein, however (0.05 . p . 0.02). T he m edian transferrin concentration was higher in the infection group than in the control group, although the mean and 95% con® dence intervals were less. Both the m ean and m edian values for tau-protein were higher in the infection group than that of the control group.
Overdrainage group O nly three CSF specim ens w ere from patients w ho developed overdrainage within the 2-m onth period and they all contained less than 0.3 g/l total protein. It was not thought that this group was large enough for a separate statistical analysis to be perform ed.
Patient distribution T he incidence of com plication com pared to the C SF concentration at the preceding operation can be seen in T able VI. T his was exam ined using the c 2 -test and the distribution was not statistically signi® cant (p . 0.5).
D iscussion V entricular shunts are at present the m ost effective treatm ent for hydrocephalus, but are prone to com -
270
H. L. Brydon et al. T ABLE III. Composition of the 91 CSF specimens from patients who did not develop shunt complications (control group)
Fraction Total protein Prealbumin Albumin a -1 Antitrypsin Haptoglobin Transferrin Tau-protein g -Globulin
Median
Mean
0.23 0.005 0.100 0.015 0.016 0.026 0.013 0.028
0.76 0.013 0.368 0.054 0.074 0.109 0.047 0.094
95% C l 0.470± 0.008± 0.230± 0.029± 0.035± 0.054± 0.032± 0.055±
1.050 0.018 0.503 0.079 0.113 0.164 0.062 0.133
Proportion of total protein 100% 2% 48% 7% 10% 14% 6% 12%
Protein measurem ents are in g/l.
T ABLE IV. C omposition of the 10 CSF specimens from patients who later developed shunt infections
Fraction Total protein Pre-albumin Albumin a -1 Antitrypsin Haptoglobin Transferrin Tau-protein g -Globulin
Median
Mean
0.51 0.004 0.245 0.029 0.024 0.062 0.046 0.059
0.67 0.007 0.349 0.044 0.038 0.090 0.064 0.074
95% CI 0.270± 0.001± 0.100± 0.014± 0.019± 0.032± 0.023± 0.043±
1.060 0.014 0.597 0.074 0.058 0.147 0.105 0.104
Proportion of total protein 100% 1% 52% 7% 6% 13% 10% 11%
Protein measurem ents are in g/l.
plications that can cause considerable m orbidity and are som etim es fatal. A shunt failure rate of 16% w ithin 1 m onth of insertion has been reported in new adult patients, 11 whereas another group found that 43%, of a total of 101 patients, required at least one revision during a 10-year follow-up. 12 Children have a higher shunt com plication rate than adults. Up to 30% of shunts failed within 12 m onths in one study, 13 while another group found that 82% of children required at least one revision w ithin 10 years 14 and som e children required m any operations (up to 13). The m ain reason for the higher shunt failure rate in children is the grow th of the child withdrawing the shunt from its ideal location. However, concern has been expressed that a high C SF protein concentration, which is more frequent in children, 15,16 m ight also increase the risk of shunt failure. 1,17 Particular concern has been expressed in neonates w ith posthaemorrhagic hydrocephalus, 3 w ho tend to have the highest CSF protein concentrations. Shunt insertions are usually deferred in this group until their CSF protein content is lower and this can som etim es take several w eeks. There are several advantages to be obtained in the earlier shunting of hyperproteinorrhachic hydrocephalic patients. It has been shown that infection w ith m ultiresistant organism s was m ore likely with a longer hospital stay before shunt insertion, 18 and this is probably related to alterations in the patients’
skin ¯ ora. 19 It would therefore be bene® cial to shunt patients as early as possible. Added to this are the advantages of not having to perform repeated invasive procedures to control the hydrocephalus, the ® nancial bene® ts of a shorter hospital stay and the convenience to the fam ily of an earlier discharge. It is not clear w hen or why the theory that a high C SF protein content would lead to shunt failure originated, but it was probably based upon isolated case reports without statistical analysis. 1± 4,20 Several of the early shunt-perfusion studies also concluded that an elevated protein was deleterious to shunt perform ance, 21,22 but they are now recognised as having poor exp erim ental design. 23 Later experim ents have not found protein to impair shunt perform ance. 23± 25 The m echanism s whereby protein has been postulated to affect shunt perform ance include (1) reduced ¯ ow due to a high CSF viscosity, 2,26,27 (2) valve sticking due to the protein, (3) protein deposition leading to occlusion of the catheter lum en, 2,20,28 and (4) a greater susceptibility to shunt infection. 4,29 T hese m echanism s have recently been investigated at our unit and none have been shown to hold in practice. W e have shown that protein has a m inim al effect on C SF viscosity, 30 and that protein does not cause valve sticking, but rather lowers the pressure at which the valves operate. 23 This is probably due to a low er CSF surface tension. 31 W e have also found that a higher protein reduces bacterial
Shunt complications and CSF proteins
271
T ABLE V. Composition of the 12 CSF specimens from patients who developed shunt obstructions
Fraction
Median
Mean
95% C l
0.380 0.003 0.200 0.018 0.046 0.049 0.019 0.053
1.490 0.011 0.898 0.075 0.187 0.110 0.051 0.155
0± 0± 0± 0± 0± 0± 0± 0±
Total protein Prealbumin Albumin a -1 Antitrypsin Haptoglobin Transferrin Tau-protein g -Globulin
3.430 0.022 2.168 0.170 0.441 0.220 0.089 0.323
Proportion of total protein 100% 1% 60% 5% 13% 7% 3% 10%
Protein measurem ents are in g/l.
T ABLE VI. Incidence of complications com pared to the CSF protein concentration at the preceding operation Protein range (g/l)
p.
None
Infection
Under 0.45 0.46± 1.0 1.05± 3.0 3.05± 6.0 Over 6.0
60 14 11 4 2
4 5 1 0 0
Total
91
10
Obstruction
Overdrainage
Total
7 3 1 0 1
3 0 0 0 0
74 22 13 4 3
12
3
116
0.5 on c 2 -testing.
adhesion to shunt m aterial, 32 and this im plies that the protein should help prevent shunt infections. W e hope to publish our studies on in vivo protein adsorption to shunts catheters in the near future, but have not found evidence of protein deposition in suf® cient am ounts to occlude the catheter lum en. T his would be exp ected as plasm a contains the sam e proteins as C SF , in a 500-fold greater concentration, w ithout any sign of precipitation. T here is, therefore, no theoretical reason why a high C SF protein should hinder shunt function. In this study we have been unable to show a signi® cant difference between the CSF total protein content of children who later developed a shunt obstruction or infection and those whose treatm ent w as uncom plicated. N ineteen of the 22 children (86% ) w ho developed shunt failure had a C SF protein of under 1.0 g/l, a ® gure that m any surgeons w ould consider acceptable for shunting. Furtherm ore, 17 of the 20 children (85% ) who were shunted with a CSF protein of over 1.0 g/l did not develop com plications. This study therefore agrees w ith our laboratory w ork, and we propose that a high CSF protein does not increase the risk of shunt m alfunction. As far as is known, there have been no sim ilar prospective studies, although in retrospective analysis no correlation has been detected between the CSF protein content and shunt infection 33 or obstruction. 34 In neither of these papers were the C SF protein values of the two groups stated. O ur study has, however, suggested that som e proteins m ay be relevant in shunt com plications.
T ransferrin, the iron transport protein, w as present in lesser am ounts in those who developed a shunt infection. A low serum transferrin has been associated with an increased risk of other infections, 35,36 and this is believed to be due to a greater am ount of iron being available to bacteria. T he other signi® cant ® nding in the shunt infection group was of an increased tau-protein concentration. Its normal role in CSF has not been clari® ed, and so it is not apparent why it should promote the developm ent of infection. How ever, tau-protein it is believed to be derived from transferrin intrathecally 37 and so there m ight be an increased rate of conversion in this group of patients. Haptoglobin, the haem oglobin binding protein, was at a signi® cantly higher concentration in the shunt obstruction group. However, free haem oglobin reduces the concentration of haptoglobin, im plying that the CSF of this group contained fewer lysed red cells. T he reason w hy haptoglobin was associated with the later developm ent of shunt obstruction was therefore unclear. Our ® ndings are supported by several clinical reports that describe shunts w orking well in patients with a C SF total protein of between 1.0 and 10 g/l. 12,38,39 O ne surgeon stated that he was aware of a shunt functioning w ith a ventricular CSF of 40 g/l protein 38 and another had inserted a ventriculoatrial shunt into a patient with a lum bar C SF containing 30 g/l protein 39 (although the lum bar protein content can be up to three tim es that of the ventricular C SF 40 ).
272
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There are also reports of shunts working badly in patients with a high CSF total protein concentration, 1,2,3,20 but these reports are brief and om it so m any im portant details that it is dif® cult to comm ent on them further. Another group attributes their low incidence of shunt obstruction in neonates to using ventricular drains in those with a protein C SF of over 1.5 g/l until the protein concentration w as lower, although they do not state what level they consider acceptable.17 Their success was offset, however, by two fatal shunt infections that were thought to be related to the use of the external drains. This raises the possibility that shunt infections that have been attributed a high CSF protein content 2,3 were actually com plications of the invasive m ethods used to low er the protein concentration. It can be argued that the reason for failing to detect an association between the total C SF protein content and shunt com plications is that the study w as not large enough ; this is an argum ent that has com plicated research into other aspects of hydrocephalus m anagem ent. 41 How ever, we do feel that w e have refuted the popular opinion that the risk of shunt failure in hyperproteinorrhachic patients is high. W e consider that there is the need for a larger prospective study in this area, w ith all patients being shunted irrespective of their CSF protein concentration. Analysis of our data suggests that any future study should involve a patient population at least four tim es greater.
4
5
6
7 8
9 10 11
12
13
14
15
C onclusions O ur study has shown that an elevated C SF protein does not predispose to shunt malfunction, and we suggest that there is no need to w ait for a high C SF protein concentration to return to norm al before inserting a shunt. H owever, laboratory work has suggested that blood cells im pair shunt performance.23 It is therefore recom m ended that patients are not shunted while their C SF is frankly bloodstained.
16
17
18
19
A cknowledgem ents W e thank the D atnow fam ily and the W ade C haritable T rust for ® nancial assistance with the project. W e also thank M s A. W ade and M s K. D rew for statistical assistance.
20
21
References 22 1 Foltz EL, Shurtleff DB. Five year com parative study of hydrocephalus in children with and without operation (113 cases). J Neurosurg 1963;20 :1064± 78. 2 Occhipinti E, Carapella C M. Shunt failure in hydrocephalus with high protein ¯ uid. M onog N eural Sci 1982;8:220± 2. 3 Scarff TB, Anderson DE, Anderson CL , Caldwell
CC. Com plications of ventriculo-peritoneal shunts in premature infants. Concepts Pediat N eurosurg 1983;4:81± 8. Lorber J, Bhat US. Posthaem orrhagic hydrocephalus. Diagnosis, differential diagnosis, treatment and longterm results. Arch Dis C hildh 1974;49 ,751± 62. Fouyas IP, Casey ATH, Thompson D, Harkness WF, Hayward RD. The use of intracranial pressure monitoring in the management of childhood hydrocephalus and shunt-related problems, N eurosurgery 1996;38: 726± 32. Luxton RW , Patel P, Keir G, Thompson EJ. A micromethod for m easuring total protein in cerebrospinal ¯ uid by using benzethonium chloride in microtitre plate wells. Clin Chem 1989;35:1731± 4. Jeppsson JO, Laurell C B, Franze n B. Agarose gel electrophoresis. C lin C hem 1979;25 :629± 38. Riches PG, Michael D, Sheldon J, Weatherald L. Sensitive colloidal m etal staining of cerebrospinal ¯ uid proteins in agarose gels. Lab Practice 1986;35 :10± 12. Laurell CB. Electroimmuno assay. Scand J C lin Lab Invest 1972;29,suppl. 124:21± 37. Brackenridge CJ. Cerebrospinal ¯ uid protein fractions in health and disease. J Clin Pathol 1962;15 :206± 10. Puca A, Anile C, M aria G, Rossi G. Cerebrospinal ¯ uid shunting for hydrocephalus in the adult: factors related to shunt revision. Neurosurgery 1991;29:822± 6. Illingworth RD, Logue V, Symon L, Uemura K. The ventriculocaval shunt in the treatment of adult hydrocephalus. Results and complications in 101 patients. J Neurosurg 1971;35:681± 5. Saint-Rose C , Piatt JH, Renier D, Pierre-Kahn A, Hirsch JF, Hoffmann HJ, Humphreys RP, Hendrick EB. M echanical com plications in shunts. Pediatr N eurosurg 1991± 2;17:2± 9. Pople IK, Quinn M W, Bayston R. Morbidity and outcome of shunted hydrocephalus. Zeitsc h K inderchir 1990;45 ,suppl. 1:29± 31. Pryce JD, PW Grant, Saul KJ. Normal concentrations of lactate, glucose, and protein in cerebrospinal ¯ uid, and the diagnostic implications of abnormal concentrations. Clin Chem 1970;16:562± 5. Widell S. On the cerebrospinal ¯ uid in normal children and in patients with acute abacterial meningo-encephalitis. Acta Paediatr 1958;47 ,suppl. 115:1± 102. Pezzotta S, Locatelli D, Bonfanti N, Sfogliarini R, Bruschi L, Rondini G. Shunt in high risk newborns. C hilds Nerv Syst 1987;3:114± 16. Etienne J, Charpin B, Grando J, Brun Y, Bes M, Fleurette J. Characterisation of clinically signi® cant isolates of Staphylococcus epiderm idis from patients with cerebrospinal ¯ uid shunt infections. Epidemiol Infect 1991;10 6:467± 75. D’ Angio C T, M cGowan KL, Baumgart S, St. Geme J, Harris M C. Surface colonisation with coagulasenegative staphylococci in premature neonates. J Pedia tr 1989;11 4:1029± 34. Wise BL, Ballard R. Hydrocephalus secondary to intracranial hem orrhage in premature infants. C hilds Brain 1976;2,234± 41. Hakim S, de la Roche FD, Burton JD. A critical analysis of valve shunts used in the treatm ent of hydrocephalus. Dev M ed Child N eurol 1973;15 :230± 55. Rayport MR, Reiss J. Hydrodynam ic properties of certain shunt assemblies for the treatment of hydrocephalus. Part 1: Report of a case of communicating hydrocephalus with increased cerebrospinal ¯ uid production treated by duplication of shunting device. Part 2: pressure-¯ ow characteristics of the Spitz-Holter, Pudenz-Heyer and Cordis-Hakim shunt systems. J Neurosurg 1969;30:455± 67.
Shunt complications and CSF proteins 23 Brydon HL, Bayston R, Hayward R, Harkness W . The effect of protein and blood cells on the ¯ owpressure characteristics of shunts. N eurosurgery 1996; 38:498± 505. 24 Pudenz RH. CSFÐ protein study. PS Medical Corporation, Goleta, M edical Education Series Pam phlet 1992. 25 Trost HA, Heissler HE, Claussen G, Gabb MR. Testing the hydrocephalus shunt valve; long term bench test results of various new and explanted valves. The need for a model for testing valves under physiological conditions. Eur J Pediatr Surg 1991;1,suppl. 1:38± 40. 26 Salm on JH. A ventriculoperitoneal shunt for hem orrhagic or high protein ¯ uid. Surg Neurol , 8:69± 70. 27 Schachter P, Findler G. Continuous spinal drainage of high viscosity CSF using IVAC system Ð technical note. A cta Neurochir (Wien) 1987:84 :71± 2. 28 Scarff JE. Treatment of hydrocephalus: an historical and critical review of methods and results. J N eurol N eurosurg Psychiatry 1963;26:1± 26. 29 M acnab GH. The development of the knowledge and treatment of hydrocephalus. Dev M ed C hild N eurol 1968;8, suppl. 11:1± 9 30 Brydon HL, Hayward R, Harkness W, Bayston R. Physical properties of cerebrospinal ¯ uid of relevance to shunt function. 1: The effect of protein upon CSF viscosity. Br J Neurosurg 1995;9:639± 44. 31 Brydon HL, Hayward R, Harkness W, Bayston R. Physical properties of cerebrospinal ¯ uid of relevance to shunt function. 2: The effect of protein upon CSF surface tension and contact angle. Br J Neurosurg 1995;9:645± 53. 32 Brydon HL, Hayward R, Harkness W, Bayston R.
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The effect of CSF proteins upon bacterial adhesion to shunt m aterial. J N eurol Neurosurg Psychiatry 1994;57 :391. Pople IK, Bayston R, Hayward RD. Infection of cerebrospinal ¯ uid shunts in infantsÐ a study of aetiological factors. J Neurosurg 1992;77 :29± 36. Overton MC , Snodgrass SR. Ventriculo-venous shunts for infantile hydrocephalus. A review of ® ve years’ experience with this method. J N eurosurg 1965;23 :517± 21. Shanbhogue LRK, Paterson N. Effect of sepsis and surgery on trace minerals. J Parenteral Enteral N utr 1990;14 :287± 9. Towns ML, Bennett B, Check IJ, Hunter RL. An improved method for determining the microbial inhibitory activity of serum and its application to the study of patients with leukemia. Am J Clin Pathol 1989;92 :192± 8. Verheecke P. On the t -protein in cerebrospinal ¯ uid. J Neurolog Sci 1975;26 :277± 81. Eckstein HB. The surgical treatm ent of hydrocephalus with the Holter valve. Turkish J Pediat 1965;7:12± 21. Forrest DM , C ooper DGW . Com plications of ventriculo-atrial shunts. A review of 455 cases. J N eurosurg 1968;29 :506± 12. Thompson EJ. Im munochemistry of CSF proteins. In: M ilford Ward A, W hicher JT (Eds) Imm unochem istry in clinical laboratory m edicine . Lancaster: M TP Press 1979;22 9± 36. Bayston R, Bannister C, Boston V, Burman R, Burns B, Cooke F, et al. A prospective random ised controlled trial of antimicrobial prophylaxis in hydrocephalus shunt surgery. Z eitsch K inderchir 1990;45 ,suppl. 1:5± 7.
