Clinical phenotypes and natural progression for motor neuron disease:Analysis from an Australian database

摘要

From 1997 to 2003 we prospectively followed a cohort of ALS/MND patients. Patients were allocated to predeterminedclinical phenotypes using the principles established in the modified El Escorial criteria. The date and region of symptomonset were carefully determined and their progression was scored using the Appel ALS rating scale. The four distinctclinical phenotypes: Global, Flail Arm, Flail Leg and Primary Lateral Sclerosis (PLS) demonstrated significantly differentrates of progression and survival times. The Global ALS/MND phenotype can present with initial symptoms in any regionand rapidly progresses to involve all segments, with symptoms due to a mixture of combined corticospinal tract and anteriorhorn cell dysfunction. The Global phenotype has the shortest survival and most rapid rate of disease progression. There wasa significant difference in survival between Global bulbar onset and cervical onset disease but no significant difference in therate of disease progression between the three Global subgroups as determined by the Appel/ALS rating scale. Flail patientshad much slower rates of progression and significantly longer survival compared to the Global phenotype. Patients withPrimary Lateral Sclerosis as expected progressed the slowest and survived the longest compared to the other clinicalphenotypes. The utility of developing a method of assigning clinical phenotypes with similar survival and diseaseprogression rates is discussed in relation to therapeutic trial design, practice benchmarking and clinico-pathologicalcorrelations.