Early Neurobehavioral Outcome After Stroke Is Related to Release of Neurobiochemical Markers of Brain Damage

Wunderlich, Michael T.; Ebert, Anne; Kratz, Torsten; Goertler, Michael; Jost, Stefan; Herrmann, Manfred

doi:10.1161/01.str.30.6.1190

Cited by 233 publications

(205 citation statements)

References 33 publications

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“…One piece of evidence which can support this hypothesis is the relationship between the degree of neuronal damage and the serum NSE level following a cerebral stroke (Cunningham et al, 1991(Cunningham et al, , 1996DeGiorgio et al, 1995DeGiorgio et al, , 1999Fogel et al, 1997;Missler et al, 1997;Martens et al, 1998;Buttner et al, 1999;Schoerkhuber et al, 1999;Wunderlich et al, 1999) or other neuronal brain damage (DeGiorgio et al, 1995(DeGiorgio et al, , 1999Fogel et al, 1997;Martens et al, 1998; Buttner et al, 1999;Schoerkhuber et al, 1999). In these diseases, the serum NSE level exhibits a prognostic indication inasmuch as studies have found a close relationship between the volume of affected neuronal tissue and the serum NSE level (Cunningham et al, 1991(Cunningham et al, , 1996Missler et al, 1997;Wunderlich et al, 1999). We hypothesize that the poor outcome of patients with a high NSE level and brain metastasis is due to the severity of normal neuronal tissue damage surrounding metastases.…”

Section: Discussionmentioning

confidence: 99%

Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO* analysis of prognostic factors

et al. 2001

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Patients with lung cancer frequently suffer from brain metastases at the time of presentation. This condition affects approximately 10% of non-small cell lung cancer (NSCLC) patients (Newman and Hansen, 1974;Sorensen et al, 1988). Surgery is feasible only for a small proportion of these patients. Whole brain radiotherapy has been, hitherto, the generally recommended treatment in inoperable patients. The survival of NSCLC patients with brain metastases is poor, reported to be between 3 to 6 months in patients treated with medical therapies, either radiotherapy or chemotherapy (compared to 6-10 months in other advanced NSCLC (Paesmans et al, 1995;Shepherd, 1999)). Furthermore, brain metastases at the time of presentation of lung cancer seems to be a worse prognosis (Sorensen et al, 1988) than metachronous brain metastases.New therapeutic strategies are needed to improve the outcome of these patients. The knowledge of prognostic determinants might be important in both clinical trials and routine practice (Komaki et al, 1993;Charloux et al, 1997;Paesmans et al, 1997;Merrill et al, 1999). In the former setting, prognostic co-variables must be taken into account in survival analyses; by way of illustration, in a given randomized trial, the statement that a difference in survival is related to the effects of the treatment must be supported by a proportional hazards model demonstrating that this effect does not depend on well-known prognostic determinants (Depierre et al, 1999;Furuse et al, 1999). In the second setting, a therapeutic decision might be influenced by the state of prognostic variables (Komaki et al, 1993).Here we especially take a look at the prognostic significance of 2 specific serum markers, CYFRA 21-1 and neuron-specific enolase (NSE). The prognostic value of CYFRA 21-1 (a fragment of cytokeratin subunit 19) in this disease has been suggested (Pujol et al, 1993;Wieskopf et al, 1995;Brechot et al, 1997). NSE, the γ-subunit of enolase, has been widely investigated as a marker of small cell lung cancer (SCLC;Jorgensen et al, 1989). Although only a small proportion of NSCLC presented with a high NSE level, this marker might indirectly reflect; i) a neuroendocrine component of the disease in favour of tumour heterogeneity; ii) a Summary A multi-centre retrospective study involving 4 French university institutions has been conducted in order to identify routine pretherapeutic prognostic factors of survival in patients with previously untreated non-small cell lung cancer and brain metastases at the time of presentation. A total of 231 patients were recorded regarding their clinical, radiological and biological characteristics at presentation. The accrual period was January 1991 to December 1998. Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The median survival of the whole population was 28 weeks. Univariate analysis (log-rank), showed that patients affected by one of the following characteristics proved to have a shorter survival in comparison with the opposite status...

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Section: Discussionmentioning

confidence: 99%

Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO* analysis of prognostic factors

et al. 2001

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“…Only median CRP levels in group H significantly decreased from 25 (22-33) to 14 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) mg/dL 3 days after study entry (PM10) and to 7 (2-13) mg/dL at the end of the observation period, but did not reach the normal range (Figure 2). Although CRP values in group H were slightly higher from PM1 (study entry) to PM8 (42 h after study entry), median 2 Serum S-100B, IL-8, and plasma PMN elastase levels, as well as serum CRP levels and fluid balance within the first 6 days of septic shock.…”

Section: S-100b/il-8 Serum and Pmn Elastase Plasma Levels After Randomentioning

confidence: 98%

“…Measurement of the neuroprotein S-100B released into the circulation was considered as a reliable procedure in detecting brain damage due to isolated traumatic brain injury (17), stroke (18), hemorrhage (19) or global ischemia (20,21). Increased S-100B serum levels have also been observed to correlate with the duration of cardiopulmonary bypass surgery (22) and the associated development of neurological complications (23,24).…”

Section: Introductionmentioning

confidence: 99%

Effect of stress doses of hydrocortisone on S-100B vs. interleukin-8 and polymorphonuclear elastase levels in human septic shock

Mussack¹,

Briegel²,

Schelling³

et al. 2005

Clinical Chemistry and Laboratory Medicine (CCLM)

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Stress doses of hydrocortisone are known to have immunomodulatory effects in patients with hyperdynamic septic shock. The prognosis correlates with the presence and severity of septic encephalopathy. However, neurological evaluation is influenced by the use of analgesia sedation during artificial ventilation. The objective of this study was to demonstrate the effect of stress doses of hydrocortisone during the initial phase of human septic shock on the serum values of the neurospecific protein S-100B in comparison to the inflammation markers interleukin (IL)-8 in serum and polymorphonuclear (PMN) elastase in plasma. A total of 24 consecutive patients, who met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock, were enrolled in this prospective, randomized, double-blind, singlecenter trial. The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. Multi-organ dysfunction syndrome was described by the Sepsis-related Organ Failure Assessment (SOFA) score. All patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/mL at study entry to 0.07 ng/mL 6 days later without significant differences compared to the placebo group. Initial IL-8 serum levels were significantly higher in the hydrocortisone group up to 12 h after study entry, and significantly decreased from 715 to 17 pg/mL at the end of the observation period. Median PMN elastase plasma levels were not affected by hydrocortisone infusion. Patients with initial S-100B *Corresponding author: Thomas Mussack, MD, Department of Surgery Innenstadt, Klinikum der Universitä t Mü nchen, Nussbaumstraße 20, 80336 Mü nchen, Germany Phone: q49-89-5160-2638, Fax: q49-89-5160-4489, E-mail: thomas.mussack@med.uni-muenchen.de serum levels )0.50 ng/mL revealed significantly higher SOFA scores up to 30 h, IL-8 serum levels up to 12 h, and PMN elastase plasma levels up to 36 h after study entry than those patients with F0.50 ng/mL. These effects were independent of the amount of fluid correction for hemodilution. Starting S-100B, IL-8 and PMN elastase values of the hydrocortisone group were within the ranges already known in patients with out-of-hospital cardiac arrest or severe traumatic brain injury. Stress doses of hydrocortisone resulted in a significant reduction in IL-8 serum, but not in S-100B serum and PMN elastase plasma concentrations in patients with hyperdynamic septic shock. For the first time, a similar extent of S-100B increase in serum of septic patients at the time of diagnosis was shown as reported for cardiac arrest or severe traumatic brain injury.

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“…The concentration of circulating CNS antigens after stroke reflects the severity of cell injury and predicts the outcome (Herrmann et al, 2000;Wunderlich et al, 1999). If these antigens were presented to lymphocytes in the proper context, an autoimmune response to brain could develop.…”

Section: Introductionmentioning

confidence: 99%

Sensitization to Brain Antigens after Stroke is Augmented by Lipopolysaccharide

Becker

Kindrick

Lester

et al. 2005

J Cereb Blood Flow Metab

113

158

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After stroke, the blood-brain barrier is transiently disrupted, allowing leukocytes to enter the brain and brain antigens to enter the peripheral circulation. This encounter of normally sequestered brain antigens by the systemic immune system could therefore present an opportunity for an autoimmune response to brain to occur after stroke. In this study, we assessed the immune response to myelin basic protein (MBP) in animals subjected to middle cerebral artery occlusion (MCAO). Some animals received an intraperitoneal injection of lipopolysaccharide (LPS; 1 mg/kg) at reperfusion to stimulate a systemic inflammatory response. At 1 month after MCAO, animals exposed to LPS were more likely to be sensitized to MBP (66.7% versus 22.2%; P ¼ 0.007) and had more profound and persistent neurologic deficits than non-LPS-treated animals. Exposure to LPS was associated with increased expression of the costimulatory molecule B7.1 early after stroke onset (P ¼ 0.009) and increased brain atrophy 1 month after MCAO (P ¼ 0.03). These data suggest that animals subjected to a systemic inflammatory insult at the time of stroke are predisposed to develop an autoimmune response to brain, and that this response is associated with worse outcome. These data may partially explain why patients who become infected after stroke experience increased morbidity.

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Early Neurobehavioral Outcome After Stroke Is Related to Release of Neurobiochemical Markers of Brain Damage

Cited by 233 publications

References 33 publications

Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO* analysis of prognostic factors

Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO* analysis of prognostic factors

Effect of stress doses of hydrocortisone on S-100B vs. interleukin-8 and polymorphonuclear elastase levels in human septic shock

Sensitization to Brain Antigens after Stroke is Augmented by Lipopolysaccharide

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