Motor Neuron Diseases

Although many use the term ‘motor neuron disease’ to refer to amyotrophic lateral sclerosis (ALS), the most common and serious of these disorders occurring in adults, there are a wide variety of different motor neuron diseases, of varying severity, affecting all ages from infancy onwards (Table 1). This death of motor neurons is a form of neurodegenerative disease and results in paralysis of the limb and swallowing muscles. This degenerative process causes various disabilities, such as inability to walk, use the arms, swallow or speak, and it may lead to death when the breathing muscles become involved. There are two types of motor neurons, the lower and the upper (Figure 1). Lowermotor neuron cell bodies are located in the anterior horn of the spinal cord and in the brainstem. Their axons branch to innervate a group of muscle fibres within the limbs, trunk, throat or face. The group of muscle fibres innervatedbya single lowermotorneuron isknownas a motor unit. When a motor unit is diseased, as in a motor neuron disease, it sometimes fires spontaneously without any voluntary or reflex stimulus, and all themuscle fibres of its motor unit contract simultaneously. This causes a visible flickering in the muscle belly known as a fasciculation, which can also be detected by electromyographic recording from the muscle. When a lower motor neuron degenerates, the muscle fibres of its motor unit atrophy due to loss of activity and trophic influences. With loss of many of the motor neurons innervating any particular muscle, the muscle will visibly waste. Thus, the clinical features of lower motor neuron loss are weakness, wasting and fasciculations. The upper motor neuron cell bodies are located in the cerebral cortex of the brain, principally in the primary motor cortex. Their axons descend through the brainstem and spinal cord in the pyramidal tracts. Many terminate on neuronal circuits which influence how lower motor neurons control movement. Some upper motor neurons,knownasBetz cells, synapsedirectlywith the lower motor neurons and are particularly responsible for controlling complex short latency movements such as individual finger movements. In addition to paralysis, upper motor neuron damage causes spastic stiffness of limb muscles, brisk tendon reflexes, and a characteristic extension of the great toe on stroking the sole of the foot, the so-called Babinski response. ALS causes degeneration both of the lower motor neurons in the spinal cord and brainstem, which directly control voluntary (striated) muscles, and of the upper motor neurons in the motor areas of the cerebral cortex, which direct and integrate the activity of these lowermotor neurons. By contrast the other forms of motor neuron disease affect either the lower motor neurons or the upper motor neurons but not both. This article focuses on ALS, also known as Lou Gehrig disease. Article