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Correlation Study With Vascular Endothelial Growth Factor

Keun-Hwa Jung, MD; Kon Chu, MD; Sang-Wuk Jeong, MD; Hee-Kwon Park, MD; Hee-Joon Bae, MD; Byung-Woo Yoon, MD, PhD

Arch Neurol. 2003;60:1613-1618.

Background  Cerebral cavernous malformations (CCMs) are reported to exhibit a wide range of dynamic patterns including growth, regression, and de novo formation, which generally show slow and steady courses. Although the pathogenesis of CCMs is not well known, vascular endothelial growth factor (VEGF) has been suggested as a possible mediating factor.

Objectives  To report CCMs showing rapid progression over a short period and to investigate these biological characteristics.

Design  Experimental study.

Setting  Tertiary referral center, neurology department.

Patient  A 40-year-old man was admitted because of a left-sided numbness, vertigo, and ataxia, which were attributed to a pontine hemorrhage. He had experienced a left-sided weakness 6 months before admission, and thereafter had complained of intermittent headache. Serial brain magnetic resonance images showed multiple intracerebral microhemorrhages throughout the cerebral hemispheres. A biopsy of the lesion confirmed the diagnosis of CCM.

Main Outcome Measures  We investigated the expression of VEGF by immunohistochemistry of the biopsy specimen. Dynamic patterns of CCMs, obtained with spin-echo magnetic resonance images with gradient-echo sequences, were compared with serial serum VEGF concentrations, determined by enzyme-linked immunosorbent assay.

Results  Immunohistochemistry of the specimen displayed increased VEGF expression. Serial magnetic resonance images during 7 months showed dynamic signal changes of the preexisting lesions and 15 de novo formations in many cortices. The VEGF level in serum increased during this dynamic period and became normal during the steady and resolving stages.

Conclusions  Cerebral cavernous malformations can be progressively deteriorating. The endothelial proliferation induced by VEGF is likely to be an important aspect of the pathogenetic mechanisms of CCMs.

From the Department of Neurology and Clinical Research Institute, Seoul National University Hospital, Seoul (Drs Jung, Chu, Park, and Yoon), and Departments of Neurology, Eulji Medical Center, Seoul (Dr Bae), and Ilsan Paik Hospital, Inje University, Ilsan (Dr Jeong), South Korea.

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