Epidemiology This is a disease commonly encountered by neurologists, with an annual incidence rate of 0.4 to 1.76 per 100,000 population. Men are affected nearly twice as often as women. Most patients are older than age 45 years at the onset of symptoms, and the incidence increases with each decade of life (Mulder et al). The disease occurs in a random pattern throughout the world except for a dramatic clustering of patients among inhabitants of the Kii peninsula in Japan and in Guam, where ALS is often combined with dementia and parkinsonism.
In approximately 10 percent of cases the disease is familial, being inherited as an autosomal dominant trait with age-dependent penetrance. The familial cases differ in their symptoms and clinical course from nonfamilial ones; as a group they have an earlier age of onset, an equal distribution in men and women, and a slightly shorter survival. Environmental associations are reported from time to time, for example, among soldiers who had served in various regions and were exposed to toxins such as agent orange. A traumatic origin of some cases has been raised on the basis of circumstantial evidence of an increased incidence in Americal and Italian Football players (Chio et al, 2005), often coincident with the tauopathy, chronic traumatic encephalopathy. These epidemiologic associations are uncertain but further exploration is warranted.
Clinical features In the most typical forms of disease, the onset is perceived by the patient as weakness in a distal part of one limb. This is noted first as an unexplained tripping from slight foot-drop, or by awkwardness in tasks requiring fine finger movements (handling buttons and automobile ignition keys), stiffness of the fingers, and slight weakness or wasting of the hand muscles on one side. In other words, features related to upper and to lower motor neuron degeneration (or both) may appear insidiously in one limb. Cramping beyond what seems natural and fasciculations of the muscles of the forearm, upper arm, and shoulder girdle may also arise. The earliest manifestation of the lower motor neuron component of this disease is sometimes volitional cramping—for example, leg cramps as the patient turns in bed during the early morning hours.
As the weeks and months pass, the other hand and arm become similarly affected with weakness, stiffness, slowness, atrophy or cramps. Before long, the triad of atrophic weakness of the hands and forearms, fasciculations, slight spasticity of the arms or legs, and generalized hyperreflexia—all in the absence of sensory change—leaves little doubt as to the diagnosis. Muscle strength and bulk diminish in parallel or there is a relative preservation of power early in the illness. Despite the amyotrophy, the tendon reflexes are notable for their liveliness. Babinski and Hoffmann signs are variably present; surprisingly, they may not appear even as the illness progresses. Abductors, adductors, and extensors of fingers and thumb tend to become weak before the long flexors, on which the handgrip depends, and the dorsal interosseous spaces become hollowed, giving rise to the “cadaveric” or “skeletal” hand. The muscles of the upper arm and shoulder girdles are typically involved later. There is a general tendency for adjacent areas to be involved before more distant ones. When an arm is the first limb affected, all this occurs while the thigh and leg muscles seem relatively normal, and there may come a time in some cases when the patient walks about with useless, dangling arms. Later the atrophic weakness spreads to the neck, tongue, pharyngeal, and laryngeal muscles, and eventually those in the trunk and lower extremities yield to the onslaught of the disease.
The affected parts may ache and feel cold, but true paresthesias, except from poor positioning and pressure on nerves, do not occur or are minor. Sphincteric control is well maintained even after both legs have become weak and spastic, but many patients acquire urinary and sometimes fecal urgency in the advanced stages of the disease. The abdominal reflexes may be elicitable even when the plantar reflexes are extensor. Extreme spasticity is rarely seen.