Fig. 1

Assessment of ALS motor phenotypes. Phenotypes of the region of onset (O1-4) are assessed by patient history. Phenotypes of propagation (PE, PL, PN) pattern are determined by follow-up of the patient history and/or neurological investigation during the disease course. Some propagation phenotypes can be classified with certainty only after 12 months of follow-up. This includes the phenotypes of late propagation (PL), including the historic descriptions of progressive bulbar palsy (PBP), flail-arm syndrome (FAS) or flail-leg syndrome (FLS), respectively. Phenotypes of the motor neuron dysfunction (M0-M3) are assessed by neurological investigation of the degree of upper (UMN) and/or lower (LMN) neuron involvement. Some motor neuron dysfunction phenotypes can be classified with certainty only after 48 months of follow-up. This includes the phenotypes of pure UMN (M1p) and LMN dysfunction (M2p) in its historic descriptions of primary lateral sclerosis (PLS) and progressive muscle atrophy (PMA). In principle, phenotypes of the motor neuron dysfunction can be changing during the complete disease course. Therefore, motor neuron dysfunction phenotypes need to be re-evaluated as the disease progresses. O1) head onset; O2) arm onset; O3) trunk onset; O4) leg onset; PE) earlier propagation; PL) later propagation; PN) propagation not yet classifiable; M0) balanced UMN and LMN dysfunction; M1d) dominant UMN dysfunction; M1p) pure UMN dysfunction; M2d) dominant LMN dysfunction; M2p) pure LMN dysfunction; M3) dissociated motor neuron dysfunction with dominant LMN and UMN dysfunction of the arms and legs. Arrow, retrospective assessment period