Figure 4.

Selective vulnerability among somatic motor neurons in ALS. In ALS, somatic motor neurons of cranial motor neurons of the oculomotor, trochlear, and abducens nuclei, which regulate eye movement, remain unaffected until the end-stage of the disease. Among spinal motor neurons, there is a differential vulnerability with fast fatigable (FF) motor neurons being highly vulnerable and degenerating before symptoms onset, with resulting muscle atrophy. Slow (S) motor neurons are affected later in the disease and compensate for the loss of FF motor neurons by sprouting and innervating vacated endplates that were previously occupied by FF motor neurons. This results in fiber type switching of muscle from fast to slow. Eventually, S motor neurons are also affected and their NMJs with muscle are disrupted and their axons retract from muscle with resulting muscle weakness and atrophy.