Estimation of Ambulation and Survival in Neurodegeneration with Brain Iron Accumulation Disorders

Abstract

BACKGROUND: Neurodegeneration with Brain Iron Accumulation (NBIA) disorder is a group of ultra-orphan hereditary diseases with very limited data on its course. OBJECTIVES: To estimate the probability of preserving ambulatory ability and survival in NBIA. METHODS: In this study, the electronic records of the demographic data and clinical assessments of NBIA patients from 2012 to 2023 were reviewed. The objectives of the study and factors impacting them were investigated by Kaplan-Meier and Cox regression methods. RESULTS: One hundred and twenty-two genetically-confirmed NBIA patients consisting of nine subtypes were enrolled. Twenty-four and twenty-five cases were deceased and wheelchair-bound, with a mean disease duration of 11 +/- 6.65 and 9.32 +/- 5 years. The probability of preserving ambulation and survival was 42.9 in 9 years and 28.2 in 15 years for classical Pantothenate Kinase-Associated Neurodegeneration (PKAN, n = 18), 89.4 in 7 years and 84.7 in 9 years for atypical PKAN (n = 39), 23 in 18 years and 67.8 in 14 years for Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN, n = 23), 75 in 20 years and 36.5 in 33 years for Kufor Rakeb Syndrome (KRS, n = 17), respectively. The frequencies of rigidity, spasticity, and female gender were significantly higher in deceased cases compared to surviving patients. Spasticity was the only factor associated with death (P value = 0.03). CONCLUSIONS: KRS had the best survival with the most extended ambulation period. The classical PKAN and MPAN cases had similar progression patterns to loss of ambulation ability, while MPAN patients had a slower progression to death. Spasticity was revealed to be the most determining factor for death.