Coarse fasciculations are usually evident in the weakened muscles but may not be noticed by the patient until the physician calls attention to them. Fasciculations are almost never the sole presenting feature of ALS—a clinical truism with which one can reassure physicians and medical students who fear, on the basis of persistent focal muscle twitching in the thumb, face, foot, periocular or periorbital muscles, that they are developing the disease.
The course of this illness, irrespective of its particular mode of onset and pattern of evolution, is progressive. There may be periods lasting weeks or months during which the patient observes no advance in symptoms but clinical changes can nonetheless be detected. Half the patients succumb within 3 years of onset and 90 percent within 6 years (Mulder et al). Several clinical variations that occur with regularity and have distinguishing clinical features are described below.
Other patterns of clinical evolution In addition to the special configurations discussed further on, there are many patterns of neuromuscular involvement other than the one just described. A leg may be affected before the hands. A foot-drop with weakness and wasting of the pretibial muscles may be incorrectly attributed to peroneal nerve compression until weakness of the gastrocnemius and other muscles betray more widespread involvement of lumbosacral neurons. In our experience, this crural amyotrophy has been less frequent than the brachial-manual type. Another variant is early involvement of thoracic, abdominal, or posterior neck muscles, the last being one of the causes of head lolling and camptocormia (forward bending of the neck and trunk) in older individuals. Yet another pattern is of early diaphragmatic weakness; such cases come to attention because of respiratory failure. A symmetrical proximal limb or shoulder-girdle amyotrophy with onset at an early age is also known and simulates muscular dystrophy (Wohlfart-Kugelberg-Welander disease, discussed later in this chapter). On several occasions we have observed a pattern involving the arm and leg on the same side, first with spasticity and then with some degree of amyotrophy; this has been called the hemiplegic or Mills variant. However, this clinical pattern more often turns out to be a result of multiple sclerosis of compression of the spinal cord from laterally, as occurs with a neurofibroma.
The first and dominant manifestations of motor neuron disease may be a spastic weakness of the legs, in which case a diagnosis of primary lateral sclerosis is tentatively made (discussed further on); only after a year or two, do the hand and arm muscles weaken, waste, and fasciculate, making it obvious that both upper and lower motor neurons are diseased. Early on, a spastic bulbar palsy with dysarthria and dysphagia, hyperactive jaw jerk and facial reflexes, but without muscle atrophy, may be the initial phase of disease.
As the disease advances, very mild distal sensory loss may be observed in the feet without explanation, but, if the sensory loss is a definite and early feature, the diagnosis must remain in doubt. Between 5 and 20 percent of cases of ALS are observed in conjunction with a frontotemporal dementia although careful testing is said to expose a larger proportion of executive or other neuropsychiatric dysfunction; less commonly there is an association with a Parkinson syndrome.