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ALS is the most common progressive motor neuron disease. It is a prime example of a neurodegenerative disease and is arguably the most devastating of the neurodegenerative disorders.


The pathologic hallmark of motor neuron degenerative disorders is death of lower motor neurons (consisting of anterior horn cells in the spinal cord and their brainstem homologues innervating bulbar muscles) and upper, or corticospinal, motor neurons (originating in layer five of the motor cortex and descending via the pyramidal tract to synapse with lower motor neurons, either directly or indirectly via interneurons) (Chap. 21). Although at its onset ALS may involve selective loss of function of only upper or lower motor neurons, it ultimately causes progressive loss of both categories of motor neurons. Indeed, in the absence of clear involvement of both motor neuron types, the diagnosis of ALS is questionable. In a subset of cases, ALS arises concurrently with frontotemporal dementia (Chap. 424); in these instances, there is degeneration of frontotemporal cortical neurons and corresponding cortical atrophy.

Other motor neuron diseases involve only particular subsets of motor neurons (Tables 429-1 and 429-2). Thus, in bulbar palsy and spinal muscular atrophy (SMA; also called progressive muscular atrophy), the lower motor neurons of brainstem and spinal cord, respectively, are most severely involved. By contrast, pseudobulbar palsy, primary lateral sclerosis (PLS), and hereditary spastic paraplegia (HSP) affect only upper motor neurons innervating the brainstem and spinal cord.

TABLE 429-1Etiology of Motor Neuron Disorders

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