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(Stroke. 1997;28:1961-1965.)
© 1997 American Heart Association, Inc.

Articles

S-100 Protein: Serum Marker of Focal Brain Damage After Ischemic Territorial MCA Infarction

Thomas Büttner, MD; Stephan Weyers, MD; Thomas Postert, MD; Reiner Sprengelmeyer, PhD; Wilfried Kuhn, MD

From the University Department of Neurology, Stroke Unit, St Josef-Hospital Bochum, Germany.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose Elevations of protein S-100 (S-100) in cerebrospinal fluid and serum have been reported after cerebral infarctions. The aim of our study was to evaluate the time course of serum S-100 concentrations after territorial middle cerebral artery (MCA) infarctions in correlation with clinical data and prognosis.

Methods S-100 serum levels were serially determined in 26 patients with an acute infarction in the territory of the MCA at day 0 (within 12 hours after onset of symptoms), day 1 (24 hours after stroke onset), and days 2, 3, 4, 5, 7 or 8, and 10 after stroke and in 26 age- and sex-matched control subjects. S-100 assays were performed using a two-site radioimmunoassay technique. The clinical status was documented using the Scandinavian Stroke Scale. The functional deficit 4 weeks after stroke onset was scored by use of the modified Rankin scale. A cranial computed tomography (CCT) was performed initially and at day 4 or 5.

Results Elevated concentrations of S-100 (>0.2 µg/L) were observed in 21 of 26 patients with MCA infarction but in none of the control subjects. S-100 levels peaked at days 2 and 3 after stroke. The S-100 concentrations in serum were significantly higher in patients with severe neurological deficits at admission, with extensive infarctions and a space-occupying effect of ischemic edema as compared with the rest of the population. S-100 values were not significantly correlated with the functional prognosis.

Conclusions Presence of S-100 in serum after ischemic stroke may be due to combined leakage out of necrotic glial cells and passage through an impaired brain-blood barrier, indicating severe ischemic cell injury. Therefore, S-100 in serum can be used as a peripheral marker of ischemic focal brain damage and may be helpful for therapeutic decisions in acute ischemic stroke.

Key Words: prognosis • blood proteins • S-100 protein • ischemic stroke • blood-brain-barrier

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The S-100 is an acidic calcium-binding protein (molecular weight, 21 000) constituting a major component of the cytosol, predominantly in astroglial cells.^{1 2 3} The protein consists of two subunits ( and ß ). S-100 ßß is present in high concentration in glial and Schwann cells, S-100 ß in glial cells and S-100 is found in striated muscles, heart, and kidney.² Recently, elevations of S-100 in CSF and serum were reported in various forms of acute brain damage.^{4 5 6 7 8 9 10 11} Concentration of S-100 in CSF is a sensitive marker of brain damage after head trauma, cerebral hypoxia, cerebral bleeding, and ischemic stroke. However, studies of S-100 in serum have enrolled only a small number of patients up to now, and the clinical significance of serum S-100 is undetermined.^{2 12} We therefore studied those proteins in the serum of patients after acute cerebral infarction and their relation to clinical and CCT findings.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
S-100 serum levels were determined in 26 patients (11 men, 15 women; mean age±SD: 71.7±14.2 years) with an acute infarction in the territory of the MCA as demonstrated by CCT. In all patients actual infarction zones were visualized on CCT. Patients with lacunar stroke were not included. Further exclusion criteria were a history of a previous stroke and/or preexisting disability. All patients were admitted to our stroke unit within 24 hours after acute stroke onset. It was possible to evaluate 10 patients within 12 hours and 16 patients between 12 and 24 hours after acute stroke onset. In all patients Doppler ultrasound of cerebral vessels, electrocardiography, and echocardiography were performed.

The serum probes were taken on day 0 (within 12 hours after onset of symptoms), day 1 (within 12 to 24 hours after stroke onset), and days 2, 3, 4, 5, 7 or 8, and 10 after stroke. The number of analyses was 10 at day 0, 26 at day 1 and day 2 each, and 24 at the time points day 3 and following days. The dropout of 2 patients occurred because of early death after acute stroke. Those 2 patients were excluded from statistical analyses of data from time points day 3 and later. The clinical findings at admission were documented by the SSS.¹³ After 4 weeks the functional status of the patients was assessed by use of the modified Rankin Scale,¹⁴ defined as the functional prognosis. CCT was performed in all patients at day 0 or 1 and in all but one at day 4 or 5. The control CCT could not be performed in 1 patient who died at day 3, but his infarction was already visible on the initial CCT. CCT scan was made by a Somatom Plus 4 (Siemens; axial planes, slices parallel to the orbitomeatal line, slice thickness 8 mm). The territory of the MCA was defined according to neuroradiological guidelines published previously.¹⁵ All CCT recordings were analyzed by the same neuroradiologist. The analysis of the initial CCT focused on the presence of early infarction signs (focal brain swelling, early hypodensity, attenuation of basal ganglia, or hyperdense MCA sign).¹⁶ The size of the infarction on the control CCT was estimated as <1/3; 1/3 to 2/3, and >2/3 of the territory of the MCA. In no case were old infarctions recognized within the territory of the actual infarction. Space-occupying effects were graded visually as ventricular compression (equal to impression of the affected side of ventricle exceeding 3 mm as compared with the contralateral ventricle) or midline shift (deviation of more than 3 mm toward the contralateral side).

Blood samples were immediately centrifuged (1500g, 10 minutes), frozen, and kept at -20° until analyzed. S-100 protein assays were performed using a two-site radioimmunoassay technique available from AB Santec Medical. The test characterizes the ß -subunit of S-100 as defined by the three monoclonal antibodies SMST12, SMSK 25, and SMSK 28. The test measures the ß - and ßß-isoforms of the protein. Each patient's sample (100 µL) and diluent (100 µL; phosphate buffer with bovine serum albumin) were incubated with a monoclonal antibody to S-100 for 1 hour. The bead was washed to remove unbound material and incubated with 200 µL of a ¹²⁵J-labeled monoclonal antibody to S-100 for 2 hours. Then the bead was washed again to remove unreacted radioactive antibody, and the bound radioactivity was measured with a gamma counter. The detection limit of the test is 0.2 g/µL. Values below this level were defined as 0.199 µg/L for further statistical analysis. Generally, healthy controls have S-100 concentrations less than 0.2 g/µL.

For comparison, the serum concentrations of S-100 were also determined in an age- and sex-matched group of 26 healthy control subjects (patients from the Department of Orthopaedics, in whom clinical investigations showed no hints for neurological or severe general diseases; criteria for age-matching: ±1 year; 11 men, 15 women; mean age: 68.3±8.6 years). Age means were not significantly different between the patient group and the control group (P=.298; t test).

In general, statistical analysis was performed using nonparametric tests because the data didn't follow a gaussian distribution. The tests used are mentioned in "Results."

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patients
In 10 patients a cardiogenic embolism was assumed to the underlying etiology because of atrial fibrillation and/or detection of a source of embolism on echocardiography. One patient had a high-grade stenosis and 1 an occlusion of the ipsilateral internal carotid artery. In 14 patients the etiology of cerebral infarction remained unclear.

The mean±SD score of the SSS at admission (day 0) was 24.1±17.1; range, 2 to 53; median, 24). Twelve patients suffered from severe stroke (SSS: <20 points), 10 from moderate stroke (SSS: 20-40 points), and 4 from mild stroke (SSS: >41 points). Four patients died during the observation period of 4 weeks, 2 of them within the first week (day 2 and 3) of the disease. The degree of disability according to the modified Rankin Scale 4 weeks after stroke was as follows: grade 0/1 (no functional deficit) in 5 patients; grade 2/3 (moderate functional disability) in 7 patients, and grade 4/5 (severe functional disability) in 10 patients.

In 9 patients early signs of ischemic infarction were detectable on the initial CCT. The control CCT at day 4/5 after acute stroke onset could be performed in 25 patients and demonstrated small infarctions (<1/3 of the MCA territory) in 7 patients, moderate extensive lesions (1/3 to 2/3 of the MCA territory) in 11 patients, and large infarctions (>2/3 of the MCA territory) in 7 patients. In 7 patients infarction zones led to ventricular compression, in another 5 patients to midline shift. In 1 patient who died at day 3 control CCT was not performed, but his infarction covering more than two thirds of the MCA territory was already detectable on the initial CCT.

Serum Level of S-100
In the reference population, S-100 was less than 0.2 µg/L in all cases. Elevated concentrations of S-100 in serum were detected in 2 of 10 patients within 12 hours after stroke onset. The number of pathological concentrations of S-100 was maximum at days 2 and 3 (day 2: 16 of 26 patients, day 3: 15 of 24 patients). In 21 patients at least one elevation of S-100 in serum was observed during the period of 10 days after acute stroke. The number of very high S-100 serum levels (>1.0 µg/L) was 0 at day 0, 5 at day 1, 7 at day 2, 5 at day 3, 6 at days 4 and 5 each, 4 at day 7/8, and 1 at day 10.

Mean S-100 serum level of stroke patients amounted to 0.25±0.15 µg/L at day 0 and increased to a maximum level of 1.80±3.30 µg/L at day 3. Mean S-100 concentrations decreased to 0.40±0.33 µg/L at day 10 (Fig 1). The S-100 levels of stroke patients and control subjects at the various time points varied beyond chance (P<.0001; Kruskal-Wallis nonparametric ANOVA). Post-hoc tests demonstrated significantly elevated S-100 levels in stroke patients at days 1 (P<.05), 2 (P<.001), 3 (P<.001), 4 (P<.005), and 5 (P<.01) (Mann-Whitney U test with Bonferroni correction for multiple comparisons) as compared with control subjects. For statistical analysis of the temporal variation of S-100 values within the stroke patient group, we compared days 1, 3, and 10. The differences of S100 within this interval were significant (P<.001; Friedman nonparametric repeated measures test). Post-hoc statistics (Wilcoxon test for paired samples with Bonferroni correction for multiple comparisons) revealed a significant increase of S-100 concentrations from day 1 to day 3 (P<.01) and a significant decrease from day 3 to day 10 (P<.01).

View larger version (13K): [in this window] [in a new window]   Figure 1. Temporal profile of S-100 serum concentrations in 26 patients with an acute territorial MCA infarction (Mean, SEM) The number of patients is 10 at day 0, 26 at days 1 and 2, and 24 at the following time points.

Clinical Aspects
S-100 at days 2, 3, 5, and 7/8 was correlated significantly with the neurological deficit at admission as assessed by SSS (P<.05; Table 1; Spearman rank correlation; probability values adjusted according to the Bonferroni method).

View this table: [in this window] [in a new window]   Table 1. Correlations Between Neurological Deficits SSS at Admission and the S-100 Serum-Concentrations at Different Time Points After Stroke Onset

The comparison of patients with extensive infarctions (>2/3 of MCA territory) on control CCT to those with less extensive infarctions (small lesions: <1/3; medium lesions: 1/3 to 2/3 of MCA territory) showed significantly increased S-100 serum levels in patients with large infarctions at days 1 (P<.05), 2 (P<.01), 4 (P<.05), 5 (P<.01), 7/8 (P<.005), and 10 (P<.001) (Mann-Whitney U test, probability values adjusted according to the Bonferroni method; Table 2). The elevation of S-100 was most pronounced in patients with space-occupying ischemic lesions leading to midline shift (Table 2). All 5 patients with midline shift presented with S-100 levels in serum exceeding 1.0 µg/L at days 2 and 3, but only 2 of 20 patients without midline shift. Those differences were significant at all time points except days 0 and 1 (Table 2; Mann-Whitney U test with Bonferroni corrections). Patients with early signs of infarction detectable on the initial CCT had increased S-100 concentrations compared with patients whose initial CCT was completely normal, but this difference was not statistically significant (Table 2).

View this table: [in this window] [in a new window]   Table 2. S-100 Serum Concentrations in Subgroups of Patients With Different CCT Findings in Ischemic MCA Infarctions: Number of Patients With S-100 Values Below 0.2 µg/L

Patients with an unfavorable functional prognosis generally had higher serum concentrations of S-100 than patients with a good prognosis (Fig 2). However, patients who died due to stroke did not present S-100 values different from those of patients with an unfavorable functional outcome. Four (of 5 total) patients who developed a "malignant cerebral edema" 2 days after acute stroke onset involving the complete MCA territory already showed S-100 values of more than 1.0 µg/L at day 1. To estimate the prognostic significance of early determination of S-100 values in stroke, we compared the S-100 concentrations at days 1 and 2 in patients with minor stroke (resulting in functional deficits graded as Rankin Scale 0 or 1) to those of patients with major stroke (Rankin Scale 2 to 5). S-100 values of both subgroups differed significantly at day 2 (P<.05; Mann-Whitney U test). However, there was no significant correlation between S-100 values and the functional prognosis (P>.05 at all time points; Spearman rank correlation).

View larger version (27K): [in this window] [in a new window]   Figure 2. Mean S-100 serum concentrations in 26 patients with an acute territorial MCA infarction. Dependence on the outcome (modified Rankin Scale) 4 weeks after acute stroke onset. The number of patients is 10 at day 0, 26 at days 1 and 2, and 24 at the following time points (number of patients in each subgroup is given on the x axis).

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Many markers of ischemic brain damage have been investigated in CSF after acute ischemic stroke, such as intracellularly located enzymes, lactate, and cAMP.^{17 18 19 20} Some of those markers showed excellent correlations with clinical findings, the extension of lesions on CCT, and the prognosis. Therefore, it has been concluded that CSF markers of ischemic metabolism do provide quantitative information about the severity of ischemic cell damage.^{18 19} Furthermore, various brain-specific proteins like myelin-basic protein, enolase, proteo-lipid protein, and myelin-associated glycoprotein have been used as CSF markers of brain injury, because leakage of those substances from damaged cells into CSF compartment can be expected.^{20 21} However, the diagnostic indication for lumbar puncture and CSF analysis is restricted to patients with an unclear neurological diagnosis, and usually diagnostic yield of CSF analysis in patients with cerebral infarction is limited. Therefore, potential serum markers reflecting the ischemic injury in stroke have attracted attention. S-100 protein has been evaluated in CSF and serum after experimental focal ischemic brain damage as well as in various forms of brain injuries.^{6 8 9 22} After experimental traumatic cerebral contusion, S-100 increases in CSF with a peak concentration reached after 7.5 hours, whereas a peak S-100 concentration increase was detected in CSF 2 to 4 days after experimental occlusion of the MCA.²² In humans, CSF levels of S-100 were increased 18 hours to 4 days after large cerebral infarctions, but there was no increase after transient ischemic attack and minor stroke.⁸ However, reports of S-100 elevations in serum after ischemic stroke are sporadic, and systematic studies on clinical correlations are lacking.

In our study of ischemic infarctions of the MCA territory, about 80% of the patients presented significantly elevated serum concentrations of S-100 in at least one serum probe during an observation period of 10 days. Mainly patients with extensive ischemic edema (rather than patients with small lesions) were characterized by high S-100 levels in serum. Extensive infarction edema usually can be detected in early CCT scanning even during the first 24 hours,²³ but early detection of hypodense lesions was not significantly correlated with excessive S-100 increase. In contrast, midline shift due to ischemic edema was associated with high S-100 serum concentrations.

The peaks of S-100 serum levels were observed at days 2 and 3 after stroke onset, in accordance with a maximum S-100 increase in CSF after experimental MCA occlusion.²² A possible explanation for this retardation of S-100 increase could be that cellular injury resulting from cerebral ischemia is a gradual process.²⁴ The temporal profile of CSF S-100 concentration after cerebral infarction is similar to that of metabolic changes of the infarcted tissue as demonstrated by animal experiments, CSF lactate concentration studies, and positron emission tomography studies.^{18 25 26} The increase of S-100 parallels the formation of ischemic brain edema.²⁷ The membrane damage immediately after cerebral ischemia results in an influx of water and sodium into the cells and constitutes the cytotoxic edema.²⁶ According to our results, this early, potentially reversible lesion is not accompanied by a release of S-100 into the blood compartment. Even patients with large infarction zones had quite normal S-100 values within the first 12 hours after stroke. One may conclude that only definite neuronal infarction including at least the partial destruction of the penumbra will result in an increase of extracellular S-100. When S-100 levels reach a maximum 2 to 3 days after stroke, irreversible morphological alterations such as tissue necrosis and neuronal death can be observed by histological examination.²⁶

Leakage of glial cells has to be accompanied by a functional impairment of the blood-brain barrier to allow the transport of S-100 from brain tissue to the vascular compartment.²⁸ Histological assessment of experimental brain infarction demonstrated tissue necrosis extending into the capillary endothelium followed by diapedesis during the first 3 days of cerebral ischemia.^{29 30} Therefore, disturbance of blood-brain barrier function has to be assumed at this stage of infarction. On the other hand, in humans an increase of CSF albumin level up to the third day after cerebral infarctions has been reported, most likely due to diapedetic activity and consecutive disruption of the CSF-blood barrier.³¹ Therefore, the presence of S-100 in serum may be the consequence of combined leakage out of necrotic glial cells and passage through an impaired blood-brain barrier, indicating severe ischemic cell injury. The increase of serum S-100 may reflect extensive cerebral edema of combined cytotoxic and vasogenic origin. Large infarction zones generally lead to serious neurological deficits in the acute stage of stroke and severe functional impairment. The consecutive increase of S-100 may indicate an unfavorable functional prognosis as well as extensive infarction zones at control CCT.

Our results show that S-100 in serum may serve as a serum marker of focal ischemic brain damage. Because of lack of specificity, S-100 cannot be regarded as a diagnostic tool for cerebral ischemia, but it may serve as a prognostic marker. However, a statistical correlation between functional prognosis and S-100 values could not be shown. The number of patients included in our study is rather small, and our results need replication. Furthermore, the prognostic significance of S-100 seems to be limited because patients who died had relatively low levels of S-100 in our study. The presence of low S-100 concentrations in deceased patients may be because of the fact that death after acute stroke is often caused by nonneurological complications such as terminal heart insufficiency, pneumonia, or pulmonary embolism.³² S-100 is not appropriate to assess the further course of the disease with respect to nonneurological complications. Whether death caused by central dysregulation due to transtentorial herniation after ischemic stroke is often associated with high S-100 levels cannot be decided on the basis of our data because only one death due to this complication occurred in our population.

S-100 can be regarded as one of many criteria (other than, clinical, neurophysiological and CCT findings) to estimate the extent of cerebral injury in acute ischemic stroke and may be appropriate for evaluating therapeutic effects of neuroprotective drugs. The design of our study does not allow clarification of whether an increase of S-100 actually precedes the development of malignant brain edema. Recently, serum levels of the neuroexcitatory amino acids glutamate and glycine have been reported as markers preceding progressive stroke.³³ The reliability of S-100 as a predictor of the further course and prognosis in acute ischemic stroke compared with standard clinical and CCT investigations has to be elucidated in further studies.

View this table: [in this window] [in a new window]   Table 3. S-100 Serum Concentrations in Subgroups of Patients With Different CCT Findings in Ischemic MCA Infarctions

	Selected Abbreviations and Acronyms

 

CCT = cranial computed tomography CSF = cerebrospinal fluid MCA = middle cerebral artery S-100 = S-100 protein SSS = Scandinavian Stroke Scale

	Footnotes

 
Correspondenceto Th. Büttner, MD, Department of Neurology, Stroke Unit; Ruhr-University Bochum, St Josef-Hospital, Gudrunstraße 56, D- 44791 Bochum, Germany.

Received October 31, 1996; revision received June 13, 1997; accepted June 13, 1997.

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				C. Foerch, B. Otto, O. C. Singer, T. Neumann-Haefelin, B. Yan, J. Berkefeld, H. Steinmetz, and M. Sitzer Serum S100B Predicts a Malignant Course of Infarction in Patients With Acute Middle Cerebral Artery Occlusion Stroke, September 1, 2004; 35(9): 2160 - 2164. [Abstract] [Full Text] [PDF]

				C.-H. Yeh, Y.-C. Wang, Y.-C. Wu, Y.-M. Lin, and P. J. Lin Ischemic preconditioning or heat shock pretreatment ameliorates neuronal apoptosis following hypothermic circulatory arrest J. Thorac. Cardiovasc. Surg., August 1, 2004; 128(2): 203 - 210. [Abstract] [Full Text] [PDF]

				V. Fazio, S. K. Bhudia, N. Marchi, B. Aumayr, and D. Janigro Peripheral detection of S100{beta} during cardiothoracic surgery: what are we really measuring? Ann. Thorac. Surg., July 1, 2004; 78(1): 46 - 52. [Abstract] [Full Text] [PDF]

				E. Stolz, T. Gerriets, A. Kluge, W.-P. Klovekorn, M. Kaps, and G. Bachmann Diffusion-Weighted Magnetic Resonance Imaging and Neurobiochemical Markers After Aortic Valve Replacement: Implications for Future Neuroprotective Trials? Stroke, April 1, 2004; 35(4): 888 - 892. [Abstract] [Full Text] [PDF]

				J. R. Lynch, R. Blessing, W. D. White, H. P. Grocott, M. F. Newman, and D. T. Laskowitz Novel Diagnostic Test for Acute Stroke Stroke, January 1, 2004; 35(1): 57 - 63. [Abstract] [Full Text] [PDF]

				H. Kinoshita, H. Iranami, K. Fujii, A. Yamazaki, M. Shimogai, K. Nakahata, Y. Hironaka, and Y. Hatano The Use of Bone Cement Induces an Increase in Serum Astroglial S-100B Protein in Patients Undergoing Total Knee Arthroplasty Anesth. Analg., December 1, 2003; 97(6): 1657 - 1660. [Abstract] [Full Text] [PDF]

				J. S. Yadav Protecting the brain:how do we measure success? J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1014 - 1016. [Full Text] [PDF]

				G. Sorci, F. Riuzzi, A. L. Agneletti, C. Marchetti, and R. Donato S100B Inhibits Myogenic Differentiation and Myotube Formation in a RAGE-Independent Manner Mol. Cell. Biol., July 15, 2003; 23(14): 4870 - 4881. [Abstract] [Full Text] [PDF]

				H. Kinoshita, M. Haba, A. Yamazaki, Y. Hironaka, H. Iranami, and Y. Hatano Increased S-100 B protein levels in a patient undergoing Cesarean delivery in the presence of prolonged hemorrhagic shock Can J Anesth, June 1, 2003; 50(6): 618 - 619. [Full Text]

				T. H. Rainer, L. K.S. Wong, W. Lam, E. Yuen, N. Y.L. Lam, C. Metreweli, and Y.M. D. Lo Prognostic Use of Circulating Plasma Nucleic Acid Concentrations in Patients with Acute Stroke Clin. Chem., April 1, 2003; 49(4): 562 - 569. [Abstract] [Full Text] [PDF]

				J.-W. Elting, G. A. Sulter, M. Kaste, K. R. Lees, H. C. Diener, M. Hommel, M. Versavel, A. W. Teelken, and J. De Keyser AMPA Antagonist ZK200775 in Patients With Acute Ischemic Stroke: Possible Glial Cell Toxicity Detected by Monitoring of S-100B Serum Levels Stroke, December 1, 2002; 33(12): 2813 - 2818. [Abstract] [Full Text] [PDF]

				W. Jordan, J. Hagedohm, J. Wiltfang, G. Laier-Groeneveld, H. Tumani, A. Rodenbeck, E. Ruther, and G. Hajak Biochemical markers of cerebrovascular injury in sleep apnoea syndrome Eur. Respir. J., July 1, 2002; 20(1): 158 - 164. [Abstract] [Full Text] [PDF]

				D. Harrington, C. H. Wong, and R. S. Bonser Neurological Complications of Aortic Surgery Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2002; 6(1): 7 - 16. [Abstract] [PDF]

				W. Gartner, W. Lang, F. Leutmetzer, H. Domanovits, W. Waldhausl, and L. Wagner Cerebral Expression and Serum Detectability of Secretagogin, a Recently Cloned EF-hand Ca2+ -binding Protein Cereb Cortex, December 1, 2001; 11(12): 1161 - 1169. [Abstract] [Full Text] [PDF]

				D. Gazzolo, M. Bruschettini, M. Lituania, G. Serra, W. Bonacci, and F. Michetti Increased Urinary S100B Protein as an Early Indicator of Intraventricular Hemorrhage in Preterm Infants: Correlation with the Grade of Hemorrhage Clin. Chem., October 1, 2001; 47(10): 1836 - 1838. [Full Text] [PDF]

				M W Agelink, J Andrich, T Postert, U Wurzinger, T Zeit, P Klotz, and H Przuntek Relation between electroconvulsive therapy, cognitive side effects, neuron specific enolase, and protein S-100 J. Neurol. Neurosurg. Psychiatry, September 1, 2001; 71(3): 394 - 396. [Abstract] [Full Text] [PDF]

				E. Appachi and E. B. Mossad Inflammatory Mediators and S-100{beta} Protein Concentrations in Neonates and Infants With Congenital Heart Disease Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2001; 5(3): 256 - 261. [Abstract] [PDF]

				N. E. Khan, A. C. De Souza, and J. R. Pepper S100 protein: its use as a marker of cerebral damage in cardiac operations Ann. Thorac. Surg., August 1, 2001; 72(2): 666 - 667. [Full Text] [PDF]

				S. A. LeMaire, J. K. Bhama, Z. C. Schmittling, P. J. Oberwalder, C. Koksoy, S. A. Raskin, P. E. Curling, and J. S. Coselli S100{beta} correlates with neurologic complications after aortic operation using circulatory arrest Ann. Thorac. Surg., June 1, 2001; 71(6): 1913 - 1919. [Abstract] [Full Text] [PDF]

				H. Jonsson, P. Johnsson, M. Birch-Iensen, C. Alling, S. Westaby, and S. Blomquist S100B as a predictor of size and outcome of stroke after cardiac surgery Ann. Thorac. Surg., May 1, 2001; 71(5): 1433 - 1437. [Abstract] [Full Text] [PDF]

				Th. Els, J. Bruckmann, G. Rohn, M. Daffertshofer, J. S. Monting, R.-I. Ernestus, and M. Hennerici Spermidine: A Predictor for Neurological Outcome and Infarct Size in Focal Cerebral Ischemia? Stroke, January 1, 2001; 32(1): 43 - 46. [Abstract] [Full Text] [PDF]

M. Herrmann, P. Vos, M. T. Wunderlich, C. H. M. M. de Bruijn, and K. J. B. Lamers Release of Glial Tissue-Specific Proteins After Acute Stroke : A Comparative Analysis of Serum Concentrations of Protein S-100B and Glial Fibrillary Acidic Protein Stroke, November 1, 2000; 31(11): 2670 - 2677.