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Grossly, the spinal cord and motor nerve roots and, less often, the motor cortex are atrophic. The histology is characterized by a degeneration of the motor neurons in the spinal cord, brainstem (nuclei of the 3rd, 4th, and 6th cranial nerves are spared), and motor cortex along with a degeneration of the corticospinal and corticobul-bar tracts (Fig. 5.20). The degeneration of the cortico-


Amyotrophic lateral sclerosis (ALS). A 68-year-old man had been diagnosed with ALS at age 58 years when he noticed weakness, some wasting, and twitching in muscles of his arm. The weakness gradually progressed, involved his legs and, by the age 66, he was bedridden. On examination, he was quadriplegic with generalized muscle wasting and fasciculations. Reflexes were hypoactive in the arms, and hyperactive with clonus and Babinski sign in the legs. Sensation was normal. Facial muscles were slightly weak, and fasciculation was present in the tongue. Speech was dysarthric. Following a 13-year clinical course, he died at age 71. A. The anterior horn of the cervical cord is depleted of motor neurons. B. The thoracic cord shows degeneration of the lateral and anterior corticospinal tracts (LFB-CV). C. The spinal motor nerve root shows axonal and myelin degeneration (Holmes stain). D. The skeletal muscle shows denervation with severely atrophic muscle fibers arranged in groups (HE).

spinal tracts is most prominent in the lower spinal cord segments, and it can be traced up through the brainstem to the internal capsule (dying-back axonal degeneration). Surviving spinal motor neurons display small eosinophilic inclusions (Bunina bodies), larger hyalin bodies, and ubiquitin-positive, filamentous, skein-like inclusions (Table 5.8). The motor nerve roots show axonal and myelin degeneration; the skeletal muscles exhibit denervation (group) atrophy (see Fig. 5.20).

Neuronal losses outside the motor system may occur in the thalamus, basal ganglia, dentate gyrus, and cerebellum. ALS may occur in association with frontotem-poral dementia and the parkinsonism-dementia complex of Guam. (See the section Extrapyramidal Diseases.)

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