Clinical prospective study of biochemical markers and evoked potentials for identifying adverse neurological outcome after thoracic and thoracoabdominal aortic aneurysm surgery

Background. Neurological deficit after repair of a thoracic or thoracoabdominal aortic aneurysm (TAA/TAAA) remains a devastating complication. The aim of our study was to investigate the clinical value of biochemical markers [S-100B, neurone-specific enolase (NSE) and lactate dehydrogenase (LD)], evoked potentials and their combinations for identifying adverse neurological outcome after TAA/TAAA surgery. Methods. From 69 patients, cerebrospinal fluid and blood samples for biochemical analysis were drawn after the induction of anaesthesia, during the cross-clamp period, 5 min, 2, 4, 6, 8, and 19 h, respectively, after reperfusion. In addition, continuous perioperative recording of motor-evoked potentials after transcranial electrical stimulation (tcMEP) and somatosensory-evoked potentials was carried out. Furthermore, neurological examinations were performed. Results. In patients with a defined decrease in lower extremity tcMEP during the cross-clamp period, we found that combinations of the serum concentrations of S-100B and tcMEP ratios at 4, 6, and 8 h after reperfusion had a positive and negative predictive value of 100% in predicting adverse neurological outcome after TAA/TAAA surgery. Furthermore, combinations of the serum concentrations of S-100B and NSE or LD at 19 h after reperfusion had both a positive and negative predictive value of 100% in identifying patients with adverse outcome after TAA/TAAA repair. Conclusions. TcMEP monitoring during TAA/TAAA surgery seems to be an effective but not completely sufficient guide in our protective multi-modality strategy. Combinations of the serum concentrations of S-100B and tcMEP ratios during the early reperfusion period might be associated with adverse neurological complications. Furthermore, biochemical markers could detect central nervous system injury on the first postoperative day and may have prognostic value

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis

.AbstractBackgroundInterferon beta is used to modify the course of relapsing multiple sclerosis. Despiteinterferon beta therapy, many patients have relapses. Natalizumab, an α4 integrinantagonist, appeared to be safe and effective alone and when added to interferonbeta-1a in preliminary studies.MethodsWe randomly assigned 1171 patients who, despite interferon beta-1a therapy, hadhad at least one relapse during the 12-month period before randomization to receivecontinued interferon beta-1a in combination with 300 mg of natalizumab (589patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks.The primary end points were the rate of clinical relapse at 1 year and the cumulativeprobability of disability progression sustained for 12 weeks, as measured by theExpanded Disability Status Scale, at 2 years.ResultsCombination therapy resulted in a 24 percent reduction in the relative risk of sustaineddisability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progressionat two years were 23 percent with combination therapy and 29 percent withinterferon beta-1a alone. Combination therapy was associated with a lower annualizedrate of relapse over a two-year period than was interferon beta-1a alone (0.34vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T2-weighted magneticresonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combinationtherapy were anxiety, pharyngitis, sinus congestion, and peripheral edema.Two cases of progressive multifocal leukoencephalopathy, one of which was fatal,were diagnosed in natalizumab-treated patients.ConclusionsNatalizumab added to interferon beta-1a was significantly more effective than interferonbeta-1a alone in patients with relapsing multiple sclerosis. Additional researchis needed to elucidate the benefits and risks of this combination treatment.(ClinicalTrials.gov number, NCT00030966.