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Abstract Number: 2764

S100B Astrocyte Protein May Serve As a Prognostic Factor in Reversible Cerebral Vasoconstrictive Syndromes

Juan J. Maya1, Vikram Puvenna2,3,4, Chanda Brennan2,3,5, Seby John6, Ken Uchino7, Leonard H. Calabrese8, Damir Janigro2,4,9,10 and Rula Hajj-Ali11, 1Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH, 2Cerebrovascular Research, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 3Neurosurgery, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 4Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 5Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 69500 Euclid Avenue S10-C, Cleveland Clinic Foundation, Cleveland, OH, 7Neurology, Cleveland Clinic Foundation, Cleveland, OH, 8Cleveland Clinic Foundation, Cleveland, OH, 9Department of Neurosurgery, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 10Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 11Rheumatology, Cleveland Clinic Foundation, Cleveland, OH

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Vasculitis

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Session Information

Title: Vasculitis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Reversible Cerebral Vasoconstriction Syndromes (RCVS) are a group of disorders characterized by acute onset of recurrent thunderclap headaches with or without neurologic deficits. Radiologically, RCVS is characterized by reversible vasoconstriction; however at a molecular level the pathophysiology is poorly understood. Blood-Brain Barrier Disruption has been linked to a variety of neurological disorders. S100B is as an astrocytic protein considered to be an important peripheral blood marker of Blood-Brain Barrier Disruption and correlates with the presence or absence of enhancements on MRI scans. S100B serum levels have been used to study Blood-Brain Barrier Disruption after traumatic brain injury, and are even being used in emergency department settings to detect traumatic brain injury. Consequently, we assessed Blood-Brain Barrier Disruption in patients with RCVS by measuring the serum levels of S100B, and tested this protein for prognostic utility and risk stratification. 

Methods:  A total of 10 patients with RCVS from the Cleveland Clinic RCVS Biologic Repository were included in this study. A sample from each patient had been obtained during the ictal phase and samples of 3 patients were also obtained during the resolution of the vasoconstriction. S100B measurements were performed using S100B ELISA (Diasorin, Stillwater, MN). RCVS data was compared to age and gender matched historical controls, and subanalyses were performed using the data from the RCVS patients with ischemic stroke (n=5), and the RCVS patients with intracranial hemorrhages (n=4). 

Results:  Mean S100B level in RCVS patients during the ictal phase was statistically higher than the mean level in the control group (mean = 0.3644 vs. mean = 0.072, p < 0.0001). When the mean S100B level of RCVS patients with ischemic stroke (mean = 0.6588) was independently compared with the control group (mean = 0.072) and with RCVS patients with intracranial hemorrhages (mean = 0.048), the level was also statistically higher (p < 0.0001 for both comparisons). There was no statistical difference in the mean level of S100B between the control group and the group with intracranial hemorrhage (p = 0.7271). The levels of S100B in 2 out of 3 patients decreased when the initial levels were compared with the follow-up levels, in average from 0.08 to 0.05. The patient with the highest S100B level (> 3 SD above the mean) had multiple ischemic strokes and ultimately expired.

Conclusion:  The elevation in S100B protein levels that was observed in RCVS patients implies that this condition can cause an alteration in the permeability of the Blood-Brain Barrier. S100B levels were higher in the ischemic stroke group as compared to the hemorrhagic group and to controls. This information implies that S100B may serve as a prognostic factor in a subgroup of RCVS patients. Furthermore, RCVS patients with intracranial hemorrhage did not have a significant increase in S100B levels, which is different from what other authors have observed in non RCVS intracranial hemorrhages. Further studies with larger number of subjects are needed in order to validate and further explore this data.


Disclosure:

J. J. Maya,
None;

V. Puvenna,
None;

C. Brennan,
None;

S. John,
None;

K. Uchino,
None;

L. H. Calabrese,
None;

D. Janigro,

Markers of Blood Brain Barrier Disruption and Methods of Using Same US 7,144,708,

9,

Peripheral Markers of Blood Brain Barrier Permeability US 6,884,591 B2,

9;

R. Hajj-Ali,
None.

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