Albert W. Teelken

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((R)) Sangtec((R)) 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.

Oxidative stress in serum and peripheral blood leukocytes in patients with different disease courses of multiple sclerosis

BackgroundThe role of oxidative stress in patients with multiple sclerosis (MS) is poorly understood.ObjectiveTo investigate oxidative stress in serum and peripheral blood leukocytes in patients with different disease courses of MS.MethodsDiene conjugate (DC) levels (a measure of lipid peroxidation), total antioxidative activity (AOA) and total antiradical activity (ARA) were measured in serum and peripheral blood leukocytes from 30 patients with benign relapsing remitting MS (BMS), 27 with secondary progressive MS (SPMS), 29 with primary progressive MS (PPMS), and 30 healthy controls. All MS patients were in a clinically stable phase.ResultsSerum DC levels were elevated in patients with BMS (p <0.05), SPMS (p <0.01) and PPMS (p <0.001). Serum total AOA and ARA were not different between MS patients and controls. Compared to controls, leukocyte DC levels were not different in each MS subgroup, but total ARA was elevated. There was a strong correlation, both in controls and MS patients, between leukocyte DC levels and leukocyte total ARA (p <0.0001) and leukocyte total AOA (p <0.0001).ConclusionOxidative stress occurs in progressive as well as benign MS. The finding that cells withstand oxidative stress, due to upregulated cellular antioxidant defence mechanisms, suggests that reactive oxygen species (ROS) formation in MS is not necessarily deleterious.

AMPA Antagonist ZK200775 in Patients With Acute Ischemic Stroke

Background and Purpose— S-100B and neuron-specific enolase (NSE) serum concentrations can be used as peripheral markers of glial cell and neuronal damage, respectively. We investigated these markers in a clinical trial with the &agr;-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) antagonist ZK200775 in acute ischemic stroke patients. Methods— In a multicenter, double-blind, randomized, placebo-controlled phase 2 trial, 61 ischemic stroke patients were treated with either placebo or active drug in a dose-finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 hours (dose group 1), and 13 patients received a total dose of 525 mg in 48 hours (dose group 2). Eleven patients received a total dose of 105 mg over a period of 6 hours (dose group 3; reduction of total dose and infusion time because of adverse events in group 2). Serum concentrations of S-100B and NSE were analyzed with the use of a monoclonal sandwich immunoluminometric assay. Neurological outcome was assessed with the National Institutes of Health Stroke Scale (NIHSS). Results— In group 2 there was a significant transient worsening in the mean NIHSS score 48 hours after the start of treatment. The mean increase was 11 points. This was due to reduction of consciousness (stupor and coma) in 8 of 13 patients. Neurological deterioration in group 2 was associated with a higher increase of S-100B concentrations, but not of NSE concentrations, than in the placebo group. The trial was stopped prematurely for safety reasons. Conclusions— The AMPA antagonist ZK200775 transiently worsened the neurological condition in patients with acute ischemic stroke. Our results suggest that in addition to neuronal dysfunction, glial cell toxicity may have occurred. It may be useful to introduce monitoring of serum markers of brain damage in phase 2 trials with glutamate receptor antagonists.

Cerebrospinal fluid oligoclonal bands and progression of disability in multiple sclerosis

Antibody‐mediated inflammation is believed to contribute to tissue injury in multiple sclerosis (MS). The majority of patients with MS have oligoclonal bands (OCB), corresponding to antibodies against a variety of antigens, in their cerebrospinal fluid (CSF). The relation of CSF OCB and disease progression in MS is uncertain. To investigate whether there is a relation between CSF OCB and a more aggressive disease course of MS, 143 patients with definite MS according to the Poser diagnostic criteria and CSF analysis at time of diagnosis were followed over a period of 5 years. There were no differences in presence or number of CSF OCB between patients with significant worsening of disability and stable patients. There were no differences in presence or number of CSF OCB between patients with stable relapsing‐remitting MS and patients developing secondary progression during follow‐up. The presence or number of CSF OCB does not seem to influence early disease progression in MS.

Peripheral blood leukocyte NO production and oxidative stress in multiple sclerosis

Background The reason for increased peripheral blood leukocyte (PBL) nitric oxide (NO) production in patients with multiple sclerosis (MS) is unknown. Objective To investigate whether PBL NO production is related to measures of oxidative stress. Methods PBL nitrite, diene conjugates (DC, a measure of undergone oxidative stress), antiradical activity (ARA) and antioxidant acitvity (AOA) were measured in 35 healthy control persons and 80 patients with MS. We investigated the correlation of these measures with a partial correlation analysis, with age as the control variable. Results There was a significant correlation in both MS patients and healthy control persons between PBL nitrite levels and PBL DC, ARA and AOA. The correlations were stronger in healthy control persons. An analysis by disease subtype showed that the correlations were present in patients with relapsing—remitting and secondary progressive MS, but absent in primary progressive MS. Conclusions PBL nitrite levels and measures of oxidative stress are closely related in MS-patients as well as in healthy control persons. Increased serum NO levels in MS may be the result of a physiologic reaction to overall oxidative stress. The differences in the strength of correlation between different disease subtypes may reflect differences in leukocyte biology. Multiple Sclerosis 2008; 14: 159—165. http://msj.sagepub.com

Determination of ammonia in cerebrospinal fluid using the indophenol direct method.

We have determined ammonia in cerebrospinal fluid (CSF) with the indophenol direct method. The results were compared with an enzymatic method. The method is very simple, and precision (coefficient of variation 1.6%) and linearity (r = 0.9999, p < 0.001) of the method are excellent. The recoveries of the method are very good (within-sample recovery: range 88-93, median 93%; between-sample recovery: 88-93, median 91%). In a population of 23 neurological patients not suffering from liver disease, the reference values ranged from 8 to 26, median 18 microM. Males and females did not differ (p = 0.5). The values obtained with the indophenol method were equal to the enzymatic method (range 9-28, median 18 microM, p = 0.6). On storage in the deep freeze (-20 degrees C), there was no change in CSF ammonia concentration for at least 1 mo. When stored at 4 degrees C (refrigerator), ammonia determinations have to be performed within 2 d. CSF storage at room temperature results in artificially elevated ammonia levels and should be avoided.

CSF oligoclonal bands and progression of disability in multiple sclerosis

Received 21 December 2007 Accepted 29 December 2007 Dear Sirs, We are thankful for Dr Deleu s interest in our study and his insightful comments regarding cerebrospinal fluid (CSF) white blood cell (WBC) counts and their possible role in progression [1]. In our sample, CSF WBC counts were available in 138 patients; 91 (66%) had WBC counts of ‡6 cells/mm. The risk of worsening of disability was significantly higher in patients with normal WBC counts (35/47; 75%) compared to patients with WBC counts ‡6 cells/mm (51/91; 56%; Fisher s exact P = 0.042). The risk of secondary progression in the following 5 years did not differ significantly between patients with or without increased WBC counts. WBC count was available in 75 patients; 15 (26%) of the 58 patients with increased WBC counts progressed to secondary progression, versus two (12%) of the 17 patients with normal WBC counts. Comparing the absolute number of WBC between the outcome groups produces similar results (data not shown). It is important to keep in mind that CSF WBC counts are much more variable than CSF oligoclonal bands. The WBC count often raises temporarily during episodes of acute demyelination. Therefore, it is more difficult to use a single CSF WBC count as a prognostic variable for the subsequent years.