Amyotrophic lateral sclerosis with numerous axonal spheroids in the corticospinal tract and massive degeneration of the cortex.

A 53-year-old woman developed bulbar palsy, spastic quadriplegia, amyotrophy, and supranuclear ophthalmoplegia, and thereafter her condition was managed with mechanical ventilation for 1 year. Her total clinical course was 6 years. The autopsy examination revealed neuronal loss with reactive astrocytosis in the precentral cortex, thalamus, mammillary body, amygdala, putamen, globus pallidus, subthalamic nucleus, and the substantia nigra, in addition to degeneration of lower motor neurons, some of which contained Bunina bodies. Along the corticospinal tract, there were severe axonal loss and numerous axonal spheroids, which were positive for phosphorylated neurofilament, ubiquitin, and synaptophysin, and lipid-laden macrophages in the centrum semiovale to the crus cerebri. Ballooned neurons, which were positive for phosphorylated neurofilament, were occasionally seen in the frontal cortex. Although in the common form of amyotrophic lateral sclerosis (ALS) both upper and lower motor neurons are mainly involved, the corticospinal tract degeneration cannot be traced rostral to the pons. The noteworthy features in our patient were the precentral cortical degeneration and axonal spheroids in the corticospinal tract rostral to the pons. It remains unclear why axonal spheroids in the corticospinal tract and precentral cortical degeneration are not observed in most ALS cases. Whether their development depends on the clinical duration, mechanical ventilator management, or some other factors remains an open question.