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INTRODUCTION

Amyotrophic lateral sclerosis (ALS) is the most common form of progressive motor neuron disease (Table 197-1). ALS is caused by degeneration of motor neurons at all levels of the CNS, including anterior horns of the spinal cord, brainstem motor nuclei, and motor cortex. Familial ALS (FALS) represents 5–10% of the total and is inherited usually as an autosomal dominant disorder.

TABLE 197-1SPORADIC MOTOR NEURON DISEASES

CLINICAL FEATURES

Onset is usually midlife, with most cases progressing to death in 3–5 years. In most societies there is an incidence of 1–3 per 100,000 and a prevalence of 3–5 per 100,000. Presentation is variable depending on whether upper motor or lower motor neurons are more prominently involved initially.

Common initial symptoms are weakness, muscle wasting, stiffness and cramping, and twitching in muscles of hands and arms, often first in the intrinsic hand muscles. Legs are less severely involved than arms, with complaints of leg stiffness, cramping, and weakness common. Symptoms of brainstem involvement include dysphagia, which may lead to aspiration pneumonia and compromised energy intake; there may be prominent wasting of the tongue leading to difficulty in articulation (dysarthria), phonation, and deglutition. Weakness of ventilatory muscles leads to respiratory insufficiency. Additional features that characterize ALS are lack of sensory abnormalities, pseudobulbar palsy (e.g., involuntary laughter, crying), and absence of bowel or bladder dysfunction. Dementia is not a component of sporadic ALS; in some families ALS is co-inherited with frontotemporal dementia characterized by behavioral abnormalities due to frontal lobe dysfunction.

PATHOPHYSIOLOGY

Pathologic hallmark 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). Although at onset ALS may involve selective loss of function of only upper or lower motor neurons, it ultimately causes progressive loss of both; the absence of clear involvement of both motor neuron types should call into question the diagnosis of ALS.

LABORATORY EVALUATION

EMG provides objective evidence of extensive muscle denervation not confined to the territory of individual peripheral nerves and nerve roots. CSF is usually normal. Muscle enzymes (e.g., CK) may be elevated.

Several types of secondary motor neuron disorders that resemble ALS are treatable (...

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