S-100 Protein Levels Research Articles

Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic–clonic seizures

Purpose: Increased concentrations of the nervous-system-specific proteins neuron-specific enolase (NSE) and S-100 protein (S-100) have been measured with lesions in the CNS. Elevated levels of serum NSE (s-NSE) have been found in status epilepticus, but also after single epileptic seizures. Because larger studies addressing cerebrospinal fluid (CSF) levels of NSE or S-100 have not been performed, we measured CSF NSE and S-100 after tonic–clonic seizures to search for evidence of neuronal and glial damage. Methods: 22 consecutive patients with single, previously undiagnosed and untreated tonic–clonic seizures were studied. Serum and CSF samples were collected within 24 h after seizure. 18 serum and CSF samples were measured from a control group. Results: The mean CSF NSE was 8.9 ng/ml (range 0–28 ng/ml) and s-NSE 8.2 ng/ml (range 5–15 ng/ml) in the patient group. The mean concentrations in the control group were 13.1 ng/ml (range 3–24 ng/ml) and 8.0 ng/ml (range 5–12 ng/ml) respectively. The mean CSF S-100 was 3.17 μg/l (range 1.45–7.02 μg/l) and serum S-100 0.05 μg/l (range 0–0.32 μg/l), and in controls 3.19 μg/l (range 1.52–5.13 μg/l) and 0.08 μg/l (range 0–0.28 μg/l). Conclusion: There were no significant differences between the mean concentrations of NSE or S-100 in CSF and serum between the epileptic group and controls. These results do not confirm the previous observation of elevated NSE-levels after tonic–clonic seizures, which argues against neuronal or glial damage after uncomplicated tonic–clonic seizures in unmedicated patients.

Comparison of serum S-100 protein levels following stroke and traumatic brain injury

Temporal changes in serum S-100 protein levels were compared between patients with ischemic stroke, transient ischemic attack (TIA) and traumatic brain injury (TBI). In addition, S-100 levels were correlated with clinical severity and outcome. Measurements were done with a LIA-mat ® Sangtec ® 100 using an automated immunoluminometric assay. Serum S-100 was measured in 21 stroke patients, 18 TIA patients and ten TBI patients on days 1 (0–24 h), 2, 3, 4, 5 or 6 and 8 or 9. In a control group of 28 healthy volunteers one measurement was done. For the stroke and TIA patients, National Institutes of Health Stroke Scale (NIHSS) scores were obtained on admission and on day 10. For the TBI patients, Glasgow Coma Scale (GCS) scores were obtained on admission and Glasgow Outcome Scale (GOS) scores were obtained after 6 months. Changes in serum S-100 levels over the first 3 days were significantly different between stroke and TBI patients ( P=0.014) and between stroke and TIA patients ( P=0.006). Peak concentrations of S-100 were most often observed on day 3 or 4 after stroke and on day 1 or 2 after TBI. In the stroke patients individual S-100 peak levels correlated well with the NIHSS score on admission ( r=0.58 P=0.014) and the change in NIHSS score between day 10 and day 1 ( r=0.65, P=0.005). In the TBI patients a good correlation between individual peak levels of S-100 and the GCS score on admission ( r=−0.81, P=0.010) and the GOS score 6 months after the trauma was found ( r=−0.87, P=0.004). We conclude that there is a significant difference in temporal changes of S-100 levels between ischemic stroke and TBI patients. This suggests different pathophysiological mechanisms. The results of this study further confirm that peak levels of serum S-100 correlate with neurological deficit resulting from either stroke or TBI.

Significance of serum protein S100 levels in screening for melanoma metastasis: does protein S100 enable early detection of melanoma recurrence?

A number of recent reports suggest serum protein S100 as a prognostic parameter in patients with metastatic melanoma. In the present study, serum protein S100 was investigated as a tumour marker for screening for melanoma metastasis in patients attending regular follow-up examinations. During the period from September 1997 to December 1998, serum protein S100 levels were measured by an immunoluminometric assay in 411 consecutive high risk melanoma patients (666 samples) and in 120 control subjects. Melanoma patients with resected primary tumours with a tumour thickness of 1.5 mm or more with resected metastasis were included in the study. Overall, 41 of the 411 patients developed metastasis during the period of observation. According to the distribution of protein S100 levels, the following different cut-off values were examined: 0.08 microg/l (95 percentile of the control group) and 0.13 microg/l (95 percentile of the group of melanoma patients without metastasis). The test efficiency for protein S100 as a diagnostic test for the detection of metastasis was highest for the cut-off value of 0.13 microg/l. In eight of the 41 patients (19.5%), elevation of protein S100 was the first sign of recurrence. Of the 41 patients with metastatic disease, 13 had elevated protein S100, giving a sensitivity of 0.32. The specificity for the detection of metastasis was 0.96. In eight of the 14 patients (57%) who developed distant metastasis, elevated S100 values were the first sign of tumour progression. In conclusion, determination of serum protein S100 levels enables earlier detection of distant metastasis in patients at high risk for metastasis. The impact on survival time needs to be investigated in follow-up studies.

Early release pattern of S100 protein as a marker of brain damage after warm cardiopulmonary bypass.

Warm blood cardioplegia may be more beneficial to the heart than cold cardioplegia, but the effects of warm cardiopulmonary bypass and warm blood cardioplegia on the brain are controversial. S100 protein is an early marker of brain damage and has been detected after cold cardiopulmonary bypass. We studied S100 concentrations in 20 patients undergoing coronary artery bypass surgery before and after warm cardiopulmonary bypass (34-37 degrees C) using warm blood cardioplegia (37 degrees C) for all patients. The peak level of S100 protein occurred immediately after warm cardiopulmonary bypass, then decreased progressively until the last measurement at 4.5 h after bypass. The peak level appears to be dependent upon the age of the patient, with the following regression equation: y = -3.2 + 0.08x, where y is S100 protein concentration in microg.l-1 and x is patient age in years. Further studies are needed to investigate the clinical significance of this early release pattern. Patient age should be taken into account when studying S100 protein levels after cardiopulmonary bypass.

Rising levels of serum S100 protein precede other evidence of disease progression in patients with malignant melanoma.

Several serum markers may be useful in the detection of metastatic melanoma, but none is in routine clinical use. To assess the validity of S100 protein as a serum marker of melanoma progression. Serum S100 protein levels were measured in 496 serum samples from 214 melanoma patients, using the Sangtec luminescence immunoassay. There were 75 patients with stage 1 melanoma, 66 initially with stage 2 melanoma, 49 initially with stage 3 melanoma and 24 with stage 4 melanoma. Serum S100 protein levels were < 0.2 microg L-1 in 71 of 75 (95%) stage 1 patients. One patient who had a normal level developed local recurrence. Fifty-eight of 66 (88%) stage 2 patients also had normal serum S100 protein levels. One with elevated levels progressed to stage 3 melanoma and five with elevated levels progressed to stage 4 disease. The remaining two with elevated serum S100 protein remained well. Thirty-five of 49 (71%) stage 3 patients had normal levels and, of these, two have progressed to stage 4 disease. Three patients with stage 3 disease had an elevated serum S100 protein level on one occasion but remained well. Eleven of 13 patients who developed stage 4 melanoma during the study had rising levels of serum S100 protein > 0.2 microg L-1 5-23 weeks before detection of melanoma progression by conventional means. Twenty-two of 24 patients with stage 4 disease throughout the study had consistently elevated serum S100 protein levels, and the two patients with normal levels were clinically disease free after surgery and chemotherapy. None of 14 control subjects with atypical naevi had elevated S100 protein levels, and only one of 11 healthy normal controls had an elevated level. Thus, rising levels of serum S100 protein are a specific and sensitive clinically relevant marker of tumour progression in melanoma patients, which precedes other evidence of melanoma recurrence.

Traumatic brain damage: serum S-100 protein measurements related to neuroradiological findings.

This study was designed to investigate the correlation between S-100 protein serum measurements and neuroradiological findings in patients with head injury. We studied 278 patients with minor, moderate, and severe head injuries and 110 controls with no history of neurological disease. The study recruited patients from three Scandinavian neurotrauma centers. Serum levels of S-100 protein were measured at admittance, and computed tomographic scans of the brain were obtained within 24 h postinjury in all patients. In a subgroup of 45 patients with minor head injuries, magnetic resonance imaging was also performed. Increased serum level of S-100 protein was detected in 108 (39%) patients, and CT scan demonstrated intracranial pathology in 25 (9%) (brain contusion n = 13, subdural hematoma n = 6, epidural hematoma n = 2, traumatic subarachnoid hemorrhage n = 2, and brain edema n = 2). The proportion of patients with detectable serum level was significantly (p < 0.01) higher among those with intracranial pathology (92%) compared to those without (34%). The negative predictive value of an undetectable S-100 serum level was 0.99. Undetectable serum level of S-100 protein predicts normal intracranial findings on CT scan. Determination of S-100 protein in serum may be used to select patients for CT scanning.

Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation

Background. Cardiopulmonary bypass seems to be a major cause for both intraoperative microemboli and cerebral hypoperfusion. This study investigates high intensive transient signals (HITS) in transcranial Doppler ultrasound (TCD) and serum levels of the neurobiochemical marker protein S-100 in patients who underwent coronary artery bypass operation without cardiopulmonary bypass (off-pump CABG) in comparison with the conventional procedure using cardiopulmonary bypass (CPB). The results are related to the neuropsychologic outcome in both surgical groups.Methods. Forty patients were randomized in 2 groups (20 conventional and 20 off-pump CABG). Neurocognitive status was assessed preoperatively and postoperatively. Venous serum levels of S-100 protein were measured before and after coronary operation, HITS were measured in the middle cerebral artery during the operation.Results. The median value of HITS was 394.5 (0 to 2217) in the conventional versus 11 (0 to 50) in the off-pump group, p less than 0.0001 (Table 1). Table 1Preoperative and Perioperative Characteristics (n = 40)legendVariableGroup A (n = 20)aGroup B (n = 20)bp ValueMeanSDMeanSDAge (years)63.87.765.66.4NSAffected vessels2.40.62.50.5NSAnastomoses proximal2.40.52.20.4NSAnastomoses distal1.20.51.10.2NSSinus rhythm (%)100…100…NSEjection fraction57.46.360.86.1NSUse of IMA graft (%)100…100…NSOperation time (min)129.736.2105.724NSCPB time (min)72.221.8………MAP (mm Hg)54.47.258.011.7NSaConventional coronary artery bypass graft.bOff-pump coronary artery bypass graft.legendCPB = cardiopulmonary bypass; IMA = internal mammary artery; MAP = mean arterial pressure; NS = not significant; SD = standard deviation.Postoperative S-100 serum levels were: 3.76 (0.13 to 11.2) μg/L (conventional) versus 0.13 (0.04 to 1.01) μg/L (off-pump), p less than 0.0001. Postoperative cognitive testing showed significantly different results with a postoperative impairment of 90% of the patients in the conventional group versus no impairment in the off-pump group.Conclusions. Cognitive impairment seems to be strongly associated to CPB and the occurrence of microemboli. The off-pump technique appears to be promising in order to eliminate the source of these neuropyschologic impairments following CABG operation.

INCREASED TYROSINE HYDROXYLASE IMMUNOREACTIVITY IN BLADDER TISSUE FROM PATIENTS WITH CLASSIC AND NONULCER INTERSTITIAL CYSTITIS

Interstitial cystitis is a chronic debilitating condition which mainly affects women. Accumulated evidence indicates that interstitial cystitis is a heterogeneous syndrome. The nonulcer subtype appears different than classic interstitial cystitis in regard to symptoms, and endoscopic and histological findings as well as response to various treatments. We further explore the neurogenic nature of this disease using indirect immunofluorescence to evaluate the presence and density of various autonomic and sensory nerve fibers. Specimens from the bladder wall of 6 patients with classic interstitial cystitis, 7 with nonulcer interstitial cystitis and 6 controls were evaluated to determine the presence and density of nerve fibers containing tyrosine hydroxylase, calcitonin gene-related peptide, neuropeptide Y and substance P using specific antibodies, and the general presence of nerve fibers using a mixture of antibodies against nerve filament, neuron specific enolase and S-100 protein. Increased density and number of nerve fibers immunoreactive for tyrosine hydroxylase were noted in interstitial cystitis cases compared to controls. Furthermore, there was a difference between classic and nonulcer disease in the overall density of nerves using the antibody mixture. Our findings indicate an altered peripheral sympathetic innervation in interstitial cystitis cases, which may be an indication of primary neurogenic etiology. The difference in nerve density observed after incubation with the antibody mixture between classic and nonulcer interstitial cystitis supports the hypothesis that the 2 forms represent separate entities.

RECRUITMENT, DISTRIBUTION AND PHENOTYPES OF MAST CELLS IN INTERSTITIAL CYSTITIS

Interstitial cystitis (IC) is a chronic disabling condition of unknown etiology. One of its major characteristics is an increase in mast cells (MC) showing signs of activation. It has been suggested that the proteinase content defines two MC types: MC(TC), containing chymase and tryptase, and MC(T), which contains tryptase but lacks chymase. Here, we investigated the MC distribution and the MC proteinase expression in IC together with the tissue expression of the major MC growth factors, stem cell factor (SCF) and interleukin-6 (IL-6). MC were enumerated in bladder specimens from patients with classic IC, nonulcer IC and controls. MC were visualized in terms of metachromasia, reflecting glycosaminoglycan content, and immunohistochemically, visualizing tryptase, chymase and IL-6 as well as the surface markers CD117 and SCF. Classic IC displayed a 6 to 10-fold increase of MC identified by proteinase content while in nonulcer IC there were twice as many MC as in controls. In contrast to nonulcer IC and controls, classic IC displayed an abundance of epithelial MC. Fewer CD117+ than proteinase+ MC were detected in IC but not in controls. Classic IC coexpressed SCF and IL-6 in the epithelium and displayed numerous SCF and IL-6+ cells in the mucosa and detrusor muscle, many of which were MC. Redistribution of MC into the epithelium and a high bladder wall MC density distinguish classic IC from nonulcer IC. Our findings suggest an SCF/IL-6-driven MC response in IC. They also indicate a downregulation of the SCF receptor in IC.

The clinical value of serum S-100 protein measurements in minor head injury: a Scandinavian multicentre study

Purpose: This study of patients with minor head injury was designed to investigate the relation of S-100 protein measurements to computed tomograpy (CT) findings and patients outcomes. Increased serum levels of this protein were hypothetized to predict intracranial pathology and increased frequency of post-concussion symptoms. Methods: One hundred and eighty-two patients were studied with Glasgow Coma Scale scores of 13-15. The study recruited patients from three Scandinavian neurotrauma centres. Serum levels of S-100 protein were measured at admittance and CT scans of the brain were obtained within 24 hours postinjury in all patients. Outcome was evaluated with the Rivermead Postconcussion Symptoms Questionnaire (RPQ) 3 months after the injury. Results: Increased serum level of S-100 protein was detected in 69 (38%) patients, and CT scan demonstrated intracranial pathology in 10 (5%) (brain contusion in seven, epidural haematoma in two, traumatic subarachnoid haemorrhage in one). The proportion of patients with detectable serum level was significantly (p < 0.01) higher among those with intracranial pathology (90%) compared to those without (35%). The negative predictive value of an undetectable S-100 level was 0.99. Sixty-two per cent reported one or more post-concussion symptoms at follow-up. A trend was observed towards an increased frequency of post-concussion symptoms among patients with detectable serum levels. Conclusions: Undetectable serum level of S-100 protein predicts normal intracranial findings on CT scan. Determination of S-100 protein in serum may be used to select patients for CT scanning. Increased S-100 serum levels may be more related to post-concussion symptoms caused by mild traumatic brain injury than to symptoms of psychological origin.

Attempting to Maintain Normoglycemia During Cardiopulmonary Bypass with Insulin May Initiate Postoperative Hypoglycemia

We attempted to develop an insulin administration protocol that maintains normoglycemia in patients undergoing cardiac surgery and to study the effects of intraoperative blood glucose management on serum levels of creatine phosphokinase isoenzyme BB (CK-BB) and S-100 protein. Twenty nondiabetic patients were randomly allocated to receive either “tight control” of blood glucose with a standardized IV insulin infusion intraoperatively (Group TC) or “no control” of blood glucose intraoperatively (Group NC). Perioperative serum levels of glucose, CK-BB, and S-100 protein were determined in all patients. Group TC patients received 90.0 ± 49.2 units of insulin, whereas Group NC patients received none. Despite insulin, both Group TC (P = 0.00026) and Group NC (P = 0.00003) experienced similar significant increases in blood glucose levels during hypothermic cardiopulmonary bypass. However, mean blood glucose level upon intensive care unit arrival was significantly decreased in Group TC, compared with Group NC (84.7 ± 41.0 mg/dL, range 32–137 mg/dL vs 201.4 ± 67.5 mg/dL, range 82–277 mg/dL, respectively; P = 0.0002). Forty percent of Group TC patients required treatment for postoperative hypoglycemia (blood glucose level <60 mg/dL). Substantial interindividual variability existed in regard to insulin resistance. The investigation was terminated after we realized that normoglycemia was unattainable with the study protocol and that postoperative hypoglycemia was unpredictable. All patients in both groups experienced similar significant increases in postoperative serum levels of CK-BB and S-100 protein. These results indicate that “tight control” of intraoperative blood glucose in nondiabetic patients undergoing cardiac surgery was unattainable with the study protocol and may initiate postoperative hypoglycemia. Implications: The appropriate intraoperative management of hyperglycemia and whether it adversely affects neurologic outcome in patients after cardiac surgery remains controversial. This investigation reveals that attempting to maintain normoglycemia in this setting with insulin may initiate postoperative hypoglycemia.

Traumatic brain damage in minor head injury: relation of serum S-100 protein measurements to magnetic resonance imaging and neurobehavioral outcome.

The present study was conducted to validate S-100 protein as a marker of brain damage after minor head injury. We studied 50 patients with minor head injuries and Glasgow Coma Scale scores of 13 to 15 in whom computed tomographic scans of the brain revealed no abnormalities. Serum levels of S-100 protein were measured at admittance and hourly thereafter until 12 hours after injury. Magnetic resonance imaging and baseline neuropsychological examinations were performed within 48 hours, and neuropsychological follow-up was conducted at 3 months postinjury. Fourteen patients (28%) had detectable serum levels of S-100 protein (mean peak value, 0.4 microg/L [standard deviation, +/- 0.3]). The S-100 protein levels were highest immediately after the trauma, and they declined each hour thereafter. At 6 hours postinjury, the serum level was below the detection limit (0.2 microg/L) in five (36%) of the patients with initially detectable levels. Magnetic resonance imaging revealed brain contusions in five patients, four of whom demonstrated detectable levels of S-100 protein in serum. The proportion of patients with detectable serum levels was significantly higher when magnetic resonance imaging revealed a brain contusion. In patients with detectable serum levels, we observed a trend toward impaired neuropsychological functioning on measures of attention, memory, and information processing speed. Determination of S-100 protein levels in serum provides a valid measure of the presence and severity of traumatic brain damage if performed within the first hours after minor head injury.

Serum levels of S-100 protein and 5-S-cysteinyldopa as markers of melanoma progression

Serum S-100 protein is widely used as a marker of melanoma and since 5-S-cysteinyldopa (5-S-CD) is a precursor of melanin its serum and urinary levels can reflect melanoma progression. In this study we examined the concentration changes of serum S-100 protein and 5-S-CD in 252 melanoma patients of different clinical stages. Serum samples were taken from 252 melanoma patients at 860 times, from June 1996 to July 1998. The serum S-100 protein was measured by the immunoluminometric assay, levels of 5-S-CD was determined by HPLC. The value of S-100 protein in patients with primary melanoma (0.11m mg/l) and in patients without symptoms (0.15 m mg/l) ranged around the normal level (0.01—0.12 m mg/l). There was a significant difference between the values of patients with or without symptoms. There was a similarly significant difference between the S-100 values of clinical Stage I (0.11 mg/l) and Stage III (2.91 mg/l) as well as between those of clinical Stage II (0.47 mg/l) and Stage III (2.91 mg/l), respectively. Analyzing the values of patients with symptoms we observed significant difference between the S-100 protein values of patients with primary tumor and those with solitary or multiple distant metastases. In case of 5-S-CD significant difference was found between clinical Stage I and III as well as clinical Stage II and III. Furthermore, there was a significant difference between the mean marker values of patients with primary tumor, lymph node, lung metastasis and clinical stage III. Copyright 1999 W.B. Saunders Company Ltd on behalf of the Arányi Lajos Foundation

Cisternal S100 protein and neuron-specific enolase are elevated and site-specific markers in intractable temporal lobe epilepsy.

In the brain, S100 protein and neuron-specific enolase (NSE) are mainly found in glial cells and neurons, respectively. We investigated concentrations of S100 protein and NSE in cisternal cerebrospinal fluid obtained during implantation of foramen ovale electrodes in eight patients with temporal lobe epilepsy (TLE). In addition, the meningeal markers cystatin-C and beta-trace as well as total protein were measured. Patients with trigeminal neuralgia (TN) undergoing glycerol rhizotomy served as controls. S100 protein and NSE levels ipsilateral to the site of seizure onset were significantly higher than in TN. Contralateral TLE values were also markedly but not significantly elevated. The meningeal markers cystatin-C and beta-trace protein as well as total protein did not differ in TLE and TN. We conclude that interictal temporal lobe dysfunction corresponds with neuronal and glial marker elevations in the extracellular space and that site-specific elevations may predict the site of seizure origin biochemically.

Serum levels of neuron-specific enolase and s-100 protein after single tonic-clonic seizures.

Serum neuron-specific enolase (s-NSE) and s-100 protein (s-100) are sensitive markers of various brain diseases. We investigated both of these markers in nine patients within 5 min, 6 h, 12 h, and 48 h after a single tonic-clonic seizure. The mean peak s-NSE level was significantly higher after 5 min (11.97 +/- 8.56 microg/l) and 48 h (10.31 +/- 8.92 microg/l, P < 0.05) than the levels of seizure-free, age-matched controls. Five patients had increased s-NSE levels regarding the upper limit of normal as mean + 3 SD. s-100 was not detected either in controls or epileptic patients. These data indicate that s-NSE in contrast to s-100 may be an in vivo marker after generalized seizures in some patients.

O11 Rising levels of serum S100 protein precede other evidence of recurrence in patients with AJCC stage 3B malignant melanoma

O11 Rising levels of serum S100 protein precede other evidence of recurrence in patients with AJCC stage 3B malignant melanoma

Do blood levels of neuron-specific enolase and S-100 protein reflect cognitive dysfunction after coronary artery bypass?

Neuron-specific enolase (NSE) and S-100 protein have been used as markers for major brain damage. Cognitive dysfunction after cardiac surgery represents subtle brain damage that is detected by neuropsychological testing. We hypothesised that blood levels of NSE and S-100 protein would increase after coronary artery bypass surgery and that the change in blood level would correlate with the change in cognitive function. We included 35 elderly patients undergoing coronary artery bypass surgery. Neuropsychological testing was performed before surgery and postoperatively at discharge from hospital and after 3 months using a neuropsychological test battery. Serum levels of NSE and S-100 protein were measured before surgery and postoperatively after 24 h and 48 h. Serum level of both NSE and S-100 protein increased significantly 24 and 48 h after coronary artery bypass. Only the increase in NSE after 24 h was found to correlate with the degree of cognitive dysfunction at discharge from hospital. The increase in S-100 protein after 24 h correlated significantly with the duration of cardiopulmonary bypass. NSE seems to be a useful blood marker for early cognitive dysfunction after coronary artery bypass surgery.

Serum S-100 Protein in Stroke and Cardiac Surgery

To the Editor: We have followed with interest the discussion regarding S-100 proteins in stroke and cardiac surgery between Drs Wong and Bonser and Drs Missler and Wiesmann. We noticed that Drs Missler and Wiesmann questioned the specificity of our Sangtec 100 LIA assay. It is correct that the validation of the Sangtec 100 LIA assay has yet to be published. A complete validation regarding specificity has, however, been performed at Sangtec Medical during development of the assay. The monoclonal antibodies used in the Sangtec 100 LIA assay are the same as in the Sangtec 100 IRMA assay, and they have been shown to be S-100B specific using the biosensor-based BIAcore system (L. Nyberg, A. Ullen, K. Haglid, E. Sandstrom, T. Stigbrand, and J. Brundell, unpublished data, 1998). In collaboration with DAKO, we have shown that recombinant human A1, A2, A4, and A6 are not detected in the Sangtec 100 LIA assay (see Figure⇓). Furthermore, calmodulin and troponin C are not measured in …

Astroglial and neuronal proteins in cerebrospinal fluid as markers of CNS involvement in Lyme neuroborreliosis.

Is Lyme neuroborreliosis, even in its early phase, a parenchymatous disorder in the central nervous system (CNS), and not merely a meningitic process? We quantified cerebrospinal fluid (CSF) levels of four nerve and glial cell marker proteins in Lyme neuroborreliosis patients with pretreatment durations of 7-240 days. All 23 patients had meningoradiculitis, and six had objective signs of encephalopathy. Glial fibrillary acidic protein (GFAp) pretreatment levels in CSF, and the light subunit of neurofilament protein (NFL) levels were related to clinical outcome and declined significantly after treatment (P < 0.001 and P < 0.01, respectively). NFL was detectable in 11 out of 22 patients, and pre- and post-treatment NFL levels were associated with the duration of neurological symptoms within 100 days prior to treatment. Neuron-specific enolase (NSE) concentrations also decreased after therapy (P < 0.001), while CSF levels of glial S-100 protein remained unchanged. The pretreatment duration of disease was related to postinfectious sequelae. GFAp, NSE and NFL levels in CSF are unspecific indicators of astroglial and neuronal involvement in CNS disease. The findings in the present study are in agreement with the hypothesis that early and late stages of Lyme neuroborreliosis damage the CNS parenchyma.

Serum S-100 Protein in Stroke and Cardiac Surgery

To the Editor: We have read with interest the articles1 2 3 and correspondence4 of Butterworth and Missler, which dicusses the correlation of S-100 protein release with cerebral infarction and hemorrhagic strokes. The authors suggest that S-100 protein levels may be a reliable index of the mass of injured brain and the patient’s prognosis and may facilitate differentiation of hemorrhagic and nonhemorrhagic strokes. However, we would like to report that this use of S-100 protein to estimate the extent of cerebral damage cannot be extrapolated to other clinical scenarios in which cerebral injury may occur. Open-heart surgery is associated with a small but significant incidence of stroke. Surgery requiring hypothermic circulatory arrest for reconstruction of the aortic arch is associated with an incidence of stroke of 5% to 12%5–7; that for coronary artery bypass grafting (CABG) is 3% to 6%.8 Several biochemical markers of cerebral injury have been investigated as potential substitutes for serial neuropsychological assessment in studies assessing different methods of cerebral protection during surgery.9 We measured serum S-100 protein in 10 patients undergoing CABG using simple mild hypothermic cardiopulmonary bypass and in 30 patient with thoracic aortic aneurysms using profound hypothermic cardiopulmonary bypass and circulatory arrest (HCA) for up to 60 …