Yuta Murakami1, Koichi Takahashi2, Kyoka Hoshi3, Hiromi Ito3, Mayumi Kanno3, Kiyoshi Saito1, Kenneth Nollet4, Yoshiki Yamaguchi5, Masakazu Miyajima6, Hajime Arai6, Yasuhiro Hashimoto7, Tatsuo Mima8. 1. Department of Neurosurgery, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan. 2. Department of Neurosurgery, Sanno Hospital, Minato-ku, Tokyo, Japan. 3. Department of Biochemistry, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan. 4. Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan. 5. Structural Glycobiology Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, Wako, Saitama, Japan. 6. Department of Neurosurgery, Juntendo University, Tokyo, Japan. 7. Department of Biochemistry, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan. Electronic address: yasuc@fmu.ac.jp. 8. Department of Neurosurgery, Sanno Hospital, Minato-ku, Tokyo, Japan. Electronic address: tatsuomima7@yahoo.co.jp.
Abstract
BACKGROUND: Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Definitive diagnosis can be difficult by clinical examinations and imaging studies. METHODS: 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. RESULTS: 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%. CONCLUSION: L-PGDS and brain-type Tf can be biomarkers for diagnosing SIH. GENERAL SIGNIFICANCE: L-PGDS and brain-type Tf biosynthesized in the brain appears to be markers for abnormal metabolism of CSF.
BACKGROUND: Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Definitive diagnosis can be difficult by clinical examinations and imaging studies. METHODS: 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. RESULTS: Comparing with non-SIHpatients, 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%. CONCLUSION:L-PGDS and brain-type Tf can be biomarkers for diagnosing SIH. GENERAL SIGNIFICANCE: L-PGDS and brain-type Tf biosynthesized in the brain appears to be markers for abnormal metabolism of CSF.
Authors: Achmed Pircher; Albert Neutzner; Margherita Montali; Andreas Huber; Hendrik P N Scholl; Jatta Berberat; Luca Remonda; Hanspeter E Killer Journal: Eye Brain Date: 2021-04-14