Quantitative evaluation of iron chelator effects on central motor and sensory tracts in superficial siderosis

Superficial siderosis (SS) is a rare neurodegenerative disease characterized by hemosiderin deposition in the central nervous system, leading to progressive neuronal degeneration. Although myelopathy is a main clinical manifestation in SS, objective biomarkers for monitoring disease progression and treatment remain unclarified. We assessed electrophysiology of central motor and sensory conduction in patients with SS before and after iron chelator administration.

In this controlled trial, we evaluated 12 patients with SS (mean follow-up: 33.6 months [range: 18.9-36.1]), who underwent dural repair, and 9 with multiple sclerosis as controls. Transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SEPs) were used to assess motor and sensory conduction, respectively. Eight patients with SS received oral iron chelator deferiprone (1,500 mg/day), whereas four underwent surgical repair without iron chelation. Primary outcomes were changes in central motor conduction time (CMCT), motor evoked potential (MEP) amplitude, and central sensory conduction time (CCT).

At baseline, 92 and 100% of patients with SS exhibited prolonged CMCT and CCT, respectively. Prolonged conduction in patients with SS was less severe than in those with multiple sclerosis (MS). Whereas MEP amplitude and the amplitude ratio of MEP to CMAP were relatively preserved in patients with SS. After 36-month iron chelator administration, statistically significant improvement of central motor conduction time was gained in patients with SS.

TMS and SEP are sensitive tools for evaluating central conduction impairment in SS. The conduction abnormality, likely caused by a different pathomechanism from that in MS, is partially recoverable by iron chelator administration. CMCT improvement demonstrates partial reversibility of impaired motor pathway and supports the therapeutic potential of iron chelator therapy in SS.