Regional Spread Pattern Affects Prognosis in Patients with Amyotrophic Lateral Sclerosis (ALS)?.

GARGIULO MONACHELLI GISELLA; JANOTA; BETTINI; RODRÍGUEZ GE; GONZALEZ DENISELLE MC; SHOESMITH C; STRONG MJ; SICA REP

Congreso; 63rd Annual Meeting of the American Academy Of Neurology. (Honolulu, Hawaii, USA April 2011).; 2011

Objective: We sought to describe spread patterns (SP) from onset to diagnosis, first region and time of initial symptom spread, and establish the contribution of SP to prognosis. Background: ALS is traditionally described as having focal clinical onset and contiguous outward spread, which appears to have preferential directionality of advance. Design/Methods: SP were retrospectively determined in 177 sporadic ALS patients at the Ramos Mejia hospital1 (2003-2009). According to patient?s history at diagnosis, 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, classic phenotypes, time onset to diagnosis (TOD), first region spread (FRS) and first region spread time (FRST). Survival was analyzed by Kaplan-Meier tarone-ware and Cox proportional hazards methods. Results: Rostro-caudal and middle interposed represented the most frequent SP with 17.5 and 21%, whereas superior and inferior interposed were both 6% of the sample. Highest median age of onset was 65 years in superior interposed and lowest was 47 in caudo-rostral patients (p=0.001). The ratio of men to women was 0.6:1 in rostro-caudal patients, compared to 1.5-3:1 in all other cases. TOD and FRST were not significantly different between groups. FRS was more frequent and slower to contiguous areas rather than to non-contiguous or distal regions. Survival curves showed worse prognosis for superior and inferior interposed patterns with a median survival of 23 and 27.5 months (p=0.02). Factors independently affecting survival were TOD and FRST; while age, riluzole use and phenotype exerted no influence. Conclusions: In this cohort, SP influenced survival. Symptom spread which skipped regions (interposed spread) occurred infrequently but was associated with a worse prognosis.  Our findings underline the importance of considering spread patterns when assessing ALS subtypes and may assist in unraveling pathogenic mechanisms of disease