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

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±161 pg/ml), increased levels of plasma MMP-9 (111.0±99.3 ng/mL) and increased MMP-9/TIMP-1 ratio (0.65±0.44) were revealed, compared to those in control subjects (SP: 620±223 pg/mL, p<0.05; MMP-9: 33.5±20.3 ng/mL, p<0.05; MMP-9/TIMP-1 ratio 0.21±0.09, p<0.005). Serum CGRP levels in AHC patients (32.6±14.4 pg/mL) were comparable to those in control subjects (37.0±17.0 pg/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.