These purely lower motor neuron amyotrophies tend to progress at a slower pace than the usual case of ALS, some patients surviving for 15 years or longer. Chio and colleagues (1985), who analyzed the factors affecting life expectancy in 155 patients with progressive muscular atrophy (PMA), found that younger patients had a more benign course: The 5-year survival was 72 percent in patients with an onset before age 50 years and 40 percent in patients with onset after age 50 years. Some of the most chronic varieties of PMA are familial. It has been revealed that the original report of a familial variety of this illness by William Osler is in a family now known to have had a mutation in the SOD1 gene, as discussed earlier. In about half the patients, the illness takes the form of a symmetrical (sometimes asymmetrical) wasting of intrinsic hand muscles, slowly advancing to the more proximal parts of the arms; less often, the legs and thighs are the sites of the initial atrophic weakness; or the proximal parts of the limbs are affected before the distal ones. Fascicular twitchings and cramping are variably present. Otherwise, they differ from ALS only in that the tendon reflexes are diminished or absent, and signs of corticospinal tract disease cannot be detected. Nonetheless, many cases of ostensible PMA are found to have indications of corticospinal tract degeneration at autopsy (Ince et al).
The main disease to be distinguished from PMA is an immune-mediated motor neuropathy that occurs with or without multifocal block of electrical conduction (see Chap. 43), and various muscle diseases that produce a similar pattern of weakness, notably, inclusion body myopathy and polymyositis. A more extensive differential diagnosis of PMA is discussed further on.
Here reference is made to a condition in which the first and dominant symptoms relate to weakness and laxity of muscles innervated by the motor nuclei of the lower brainstem, that is muscles of the jaw, face, tongue, pharynx, and larynx. This weakness gives rise to an early defect in articulation, in which there is difficulty in the pronunciation of lingual (r, n, l), labial (b, m, p, f), dental (d, t), and palatal (k, g) consonants. As the condition worsens, syllables lose their clarity and run together, until, finally, the patient’s speech becomes unintelligible. In other patients, slurring is a result of spasticity of the tongue, pharyngeal, and laryngeal muscles; the speech sounds as if the patient were eating food that is too hot. Usually the voice is modified by a combination of atrophic and spastic weakness. Defective modulation with variable degrees of rasping and nasality is another characteristic. The pharyngeal reflex is lost, and the palate and vocal cords move imperfectly or not at all during attempted phonation. Mastication and deglutition become impaired; the bolus of food cannot be manipulated and may lodge between the cheek and teeth and the pharyngeal muscles do not force it properly into the esophagus. Liquids and small particles of food find their way into the trachea or nose. The facial muscles, particularly of the lower face, weaken and sag. Fasciculations and focal loss of tissue of the tongue are usually early manifestations; eventually the tongue becomes shriveled and lies useless on the floor of the mouth. The chin may also quiver from fascicular twitchings, but the diagnosis should not be made on the basis of fasciculations alone, in the absence of weakness and atrophy.