Regional spread pattern affects prognosis in patients with amyotrophic lateral sclerosis (ÄLS)

GARGIULO MONACHELLI GM; BETTINI M; SICA REP; SHOESMITH C; STRONG MJ

Jornada; J. Allyn Taylor. International Prize in Medicine. Imaging of the Aging Brain. The University of Western Ontario; 2010

Background and Objectives: ALS comprises focal onset and contiguous spread. We sought to describe spread patterns (SP) from disease onset to diagnosis, compare them with phenotypes and establish their contribution to prognosis. Methods: Patterns of spread and phenotypes were retrospectively determined in 177 sporadic ALS patients at the Ramos Mejia hospital1 (2003-2009). We established 8 SP: rostro-caudal (bulbar to cervical to lumbar), caudo-rostral, crossed, circular, superior interposed (bulbar to lumbar to cervical), middle interposed (cervical to bulbar to lumbar, or cervical to lumbar to bulbar) inferior interposed (lumbar to bulbar to cervical) and isolated patterns. Variables studied were age, gender, time onset to diagnosis (TOD), first region spread (FRS) and first region spread time (FRST). Survival was analyzed by Kaplan-Meier log-rank and Cox proportional hazards. Results: Among phenotypes, age was higher in bulbar (ANOVA p=0.02), and among SP, in superior interposed (p=0.001). Gender was predominantly masculine, except in bulbar, PMA and rostro-caudal patients. TOD and FRST were not significantly different among both groups. FRS was more frequent and slower to contiguous areas than non-contiguous. Survival curves showed worse prognosis for both superior and inferior interposed patterns (p=0.02) with a median of 23 and 27.5 months. Factors independently affecting survival were TOD and FRST; while age, riluzole and phenotype exerted no influence. Conclusion: In this cohort, SP influenced survival. Initial spreading to distant -interposed- regions occurred faster and determined a worse prognosis. Our findings underline the importance of considering clinical spread to assess ALS subtypes and unravel pathogenic mechanisms of disease.