APP is primarily a disease of the motor unit. However, in fatal cases, lesions are also found in the cerebral cortex, primarily in the precentral gyrus, hypothalamus, thalamus, motor nuclei of the brainstem, reticular formation, vestibular nuclei, roof nuclei of the cerebellum, and neurons in the intermediate columns.[3] During APP, motor neuron invasion may result in either motor neuron lysis or injury, with partial or complete recovery.[2] Motor neuron death causes denervation of muscle fibers, with resultant loss of voluntary activation of these fibers. If only a few motor neurons innervating a muscle are destroyed, no weakness may be perceived by the patient. Pathology studies have revealed that up to 20% of motor neurons may be destroyed in limbs with normal muscle function or only minimal paralysis.[4-6] A more severe loss of motor neurons may result in greater weakness or complete loss of muscle contraction.

Recovery of muscular force after APP can occur by collateral innervation through sprouting from remaining motor neurons or by muscle fiber hypertrophy of innervated muscle. Sprouting can produce reinnervation of locally denervated muscle fibers with restoration of the ability to produce a muscle contraction. Even with a loss of 50% of motor neurons supplying a muscle, the surviving motor neurons can achieve complete reinnervation, resulting in normal muscle strength.[7] Muscle biopsy studies have shown that the remaining motor neurons may innervate up to eight times the normal number of muscle fibers after recovery from APP.[8] In addition to motor neuron sprouting, muscle fiber hypertrophy can produce further recovery of muscular force after this illness.[9]