Profiles of blood biomarkers in alternating hemiplegia of childhood – Increased MMP-9 and decreased substance P indicates its pathophysiology

Inui, Takehiko; Saito, Yoshiaki; Sakuma, Hiroshi; Hatakeyama, Hideyuki; Goto, Yu-ichi; Arai, Hidee; Sasaki, Masayuki

doi:10.1016/j.braindev.2011.04.008

« Previous Next »Brain and Development
Volume 34, Issue 3 , Pages 196-200, March 2012

Profiles of blood biomarkers in alternating hemiplegia of childhood – Increased MMP-9 and decreased substance P indicates its pathophysiology

Takehiko Inui
- Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan
Yoshiaki Saito
- Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan
- Corresponding author. Tel.: +81 42 341 2711; fax: +81 42 346 1705.
Hiroshi Sakuma
- Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan
- Department of Immunology, National Institute of Neuroscience (NIN), NCNP, Tokyo, Japan
Hideyuki Hatakeyama
- Department of Mental Retardation and Birth Defect Research, NIN, NCNP, Tokyo, Japan
Yu-ichi Goto
- Department of Mental Retardation and Birth Defect Research, NIN, NCNP, Tokyo, Japan
Hidee Arai
- Department of Neurology, Chiba Children’s Hospital, Chiba, Japan
Masayuki Sasaki
- Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan

Received 14 February 2011; received in revised form 23 March 2011; accepted 10 April 2011. published online 09 May 2011.

Abstract

Alternating hemiplegia of childhood (AHC) is a rare disorder characterized by repeated plegic attacks, movement disorders, autonomic phenomena, and developmental delay. To obtain insights into the pathophysiology of AHC, we determined the concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of MMP-1 (TIMP-1), calcitonin gene-related peptide (CGRP), and substance P (SP) in the serum/plasma of AHC patients (n=6) and control subjects (n=11) by performing enzyme-linked immunosorbent assay (ELISA).

Decreased levels of serum SP (382±161pg/ml), increased levels of plasma MMP-9 (111.0±99.3ng/mL) and increased MMP-9/TIMP-1 ratio (0.65±0.44) were revealed, compared to those in control subjects (SP: 620±223pg/mL, p<0.05; MMP-9: 33.5±20.3ng/mL, p<0.05; MMP-9/TIMP-1 ratio 0.21±0.09, p<0.005). Serum CGRP levels in AHC patients (32.6±14.4pg/mL) were comparable to those in control subjects (37.0±17.0pg/mL). Increased MMP-9 levels may be linked to the vascular insult and is common in migraineurs. However, because AHC patients showed different changes in SP and CGRP levels compared to those shown by migraineurs, these results suggest that AHC has a pathomechanism different from the hypothesis of trigeminovascular theory. Decreased SP may represent the autonomic dysfunction in AHC, for which an etiology with progressive neuronal damage can be hypothesized.