Which phenotypes of motor neuron symptoms of ALS can be distinguished?

In classic ALS (M0), symptoms of both the first and second motor neuron occur. This means slowed and uncoordinated movements, increased reflexes and muscle stiffness (spasticity) due to the first motor neuron and muscle weakness and muscle atrophy due to the second motor neuron.

If the symptoms of the first motor neuron dominate, the phenotype is referred to as M1d. These patients show only mild symptoms of the second motor neuron. In M1p, only (“pure”) symptoms of the first motor neuron occur, without signs of the second motor neuron. After 48 months of disease progression, this form is referred to as primary lateral sclerosis (PLS).

Conversely, there are also forms in which the second motor neuron dominates. In M2d, the symptoms of the second motor neuron are much more pronounced, while those of the first motor neuron are only discretely present. In M2p, only symptoms of the second motor neuron occur. This phenotype is also known as progressive muscular atrophy (PMA).

A special form is M3, in which the symptoms are distributed differently between the arms and legs. In this case, the symptoms of the second motor neuron dominate in the arms (muscle weakness and atrophy), while the legs are mainly characterized by symptoms of the first motor neuron. This form is also known as the brachial-atrophic paraspastic phenotype.