Tight-junction proteins could help pin down hemorrhagic transformation risk

By Eleanor McDermid, Senior medwireNews Reporter

Study findings suggest that measuring levels of tight-junction proteins in the blood of patients with stroke may help to gauge their risk for hemorrhagic transformation (HT).

Admission blood levels of tight-junction proteins - cell adhesion molecules crucial to the integrity of the blood-brain barrier - varied significantly between patients according to whether they later developed HT, report Radoslaw Kazmierski (Poznan University of Medical Sciences, Poland) and colleagues.

In an editorial accompanying the study in Neurology, Glen Jickling (University of California at Davis, Sacramento, USA) and Bogdan Manolescu (Polytechnic University of Bucharest, Romania) say: "Whether a plasma biomarker of HT stroke will have clinical applications remains unclear.

"There are several practical challenges that a biomarker of HT in ischemic stroke must overcome, including a need for very high sensitivity and specificity, and a need to provide rapid results, preferably within 4.5 hours of stroke onset."

The study included 373 patients who had stroke without symptomatic HT and 33 who had a deterioration of at least 4 points on the National Institutes of Health Stroke Scale plus evidence of HT on brain imaging. None of the patients underwent thrombolysis.

Overall, levels of the tight-junction protein occludin and the ratio of claudin 5 to zonula occludens (ZO)1 were significantly higher in patients with HT than in those without. The accuracy of these markers for distinguishing between patients with and without HT, based on receiver operating characteristic curve analysis, was 62.2% and 63.4%, respectively.

Negative predictive values were high, at around 95%, but positive predictive values were low, at about 12%.

Occludin levels and the claudin 5/ZO1 ratio both increased within 4.5 hours of stroke onset (ie, within the therapeutic window for thrombolysis), as did levels of the indirect blood-brain barrier permeability marker S100B.

Among patients admitted within 3 hours of stroke (seven with HT), claudin 5 levels were significantly higher in those with than without HT. Among those admitted within 4.5 hours (12 with HT), an increased claudin 5/ZO1 ratio was associated with HT.

"Though further evaluation is required, it seems unlikely that a plasma marker of HT will achieve a sufficient positive predictive value to withhold tissue plasminogen activator from a stroke patient who is otherwise eligible," say Jickling and Manolescu. "A potentially more feasible approach is to identify ischemic strokes at increased risk for HT in whom a second agent could be coadministered with thrombolytic to prevent HT."

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