Fig. 1
Diagram of the motor system
Amyotrophic lateral sclerosis is a chronic progressive disease of the central nervous system. It affects the part of the nervous system that is responsible for voluntary control of the skeletal musculature. It involves damage to the motor nerve cells (motor neurons, motoneurons) in the brain and spinal cord.
This nerve cell including its axon is called the first motor neuron (Fig. 1: red nerve cell).
The axon of the first motor neuron makes contact with motor nerve cells in the spinal cord, which are called the second motor neurons (Fig. 1: yellow nerve cell). The nerve cells in the spinal cord are connected to the muscles through long axons.
In ALS both motor neurons, that is, the first and second motoneurons, are diseased. Destruction of the individual motor nerve cells occurs. Damage to the motor neurons is probably already present many years and possibly even decades before the onset of the neurological symptoms. Slow degeneration of the motoneurons is accompanied by typical deposits in the nerve cells (Fig. 2).
Fig. 2
Morphological features of ALS in the form of intraneural inclusions:
1.) Bunina bodies: inclusions typical of ALS, which are demonstrated by anti cystatin antibodies;
2 4.) Skein like inclusions, which are caused by accumulations of neurofilaments and are demonstrated by anti ubiquitin antibodies.
A disorder of the motor neurons is therefore first apparent to the patient as muscle weakness (diminished power, paresis), muscle wasting (atrophy) or stiffness (spasticity). Damage to the first motor neuron can lead to an uncontrolled increase in muscle tension, which the patient perceives as stiffness (spasticity). Damage to the second motoneuron diminishes activation of the muscles by the nervous system. This is followed by muscle weakness (paresis) and muscle wasting (atrophy). It is very characteristic of ALS that all of these motor symptoms exist side by side. Thus, increased reflexes or preserved intrinsic muscle reflexes can be found in paretic groups of muscles. A doctor trained in neurology can identify this combination of signs on physical examination and they are an important basis for formulating the clinical diagnosis of ALS.
Control of the muscles is a highly complicated process. Basically, two different groups of motor nerve cells are responsible (see Fig. 1). The higher cells are located in the cerebral cortex (motor cortex) and are the origin of a long nerve process (axon), which extends as far as the spinal cord.