Spontaneous intracranial hypotension is diagnosed by a combination of lipocalin-type prostaglandin D synthase and brain-type transferrin in cerebrospinal fluid

• Published in: Biochimica et biophysica acta. General subjects 2018-08, Vol.1862 (8), p.1835-1842
• Main Authors: Murakami, Yuta, Takahashi, Koichi, Hoshi, Kyoka, Ito, Hiromi, Kanno, Mayumi, Saito, Kiyoshi, Nollet, Kenneth, Yamaguchi, Yoshiki, Miyajima, Masakazu, Arai, Hajime, Hashimoto, Yasuhiro, Mima, Tatsuo
• Format: Article
• Language: English
• Subjects: Biomarker; Cerebrospinal fluid leakage; Intracranial hypotension syndrome; Lipocalin-type prostaglandin D synthase; Transferrin
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2018.03.027

Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Definitive diagnosis can be difficult by clinical examinations and imaging studies. SIH was diagnosed with the following criteria: (i) evidence of CSF leakage by cranial magnetic resonance imaging (MRI) findings of intracranial hypotension and/or low CSF opening pressure; (ii) no recent history of dural puncture. We quantified CSF proteins by ELISA or Western blotting. Comparing with non-SIH patients, SIH patients showed significant increase of brain-derived CSF glycoproteins such as lipocalin-type prostaglandin D synthase (L-PGDS), soluble protein fragments generated from amyloid precursor protein (sAPP) and “brain-type” transferrin (Tf). Serum-derived proteins such as albumin, immunoglobulin G, and serum Tf were also increased. A combination of L-PGDS and brain-type Tf differentiated SIH from non-SIH with sensitivity 94.7% and specificity 72.6%. L-PGDS and brain-type Tf can be biomarkers for diagnosing SIH. L-PGDS and brain-type Tf biosynthesized in the brain appears to be markers for abnormal metabolism of CSF. •Diagnostic markers for spontaneous intracranial hypotension (SIH) were found in cerebrospinal fluid (CSF).•The best marker combination is lipocalin-type prostaglandin D2 synthetase (L-PGDS) and “brain-type” transferrin (Tf).•L-PGDS and brain-type Tf changes were correlated with clinical tests, intracranial hypotension and residual radioisotope test