Historical Aspects of Lower Motor Neuron Syndromes

The original descriptions of pure motor syndromes without upper motor neuron signs were probably cases of "progressive muscular atrophy" in the writings of Duchenne, Aran and others during the 19th century . Benign, focal motor neuron disorders, such as monomelic amyotrophy, were subsequently reported . These syndromes were usually considered as variants of ALS, as early pathological studies suggested that the primary focus of the disease was on cell bodies in the ventral horn.
A pathological report by Rowland et al. first documented that a patient with a pure motor syndrome could have the primary site of disease along the course of the axon. This patient, with a lower motor neuron (LMN) syndrome and a serum IgM M-protein, had damage to motor axons but not cell bodies. Motor neuropathies were first diagnosed during life by electrodiagnostic testing. Nerve conduction studies showed blockade of impulses at focal sites along the course of motor axons (motor conduction block) providing strong evidence that the primary site of disease lay in the peripheral nerve rather than the cell body. The phenomenon of conduction block had been described earlier in patients with sensory-motor neuropathies (chronic inflammatory demyelinating polyneuropathy (CIDP)) . Conduction block was thought to result from focal regions of immune-mediated demyelination along the course of the nerve.
In 1986 a patient was reported with a LMN syndrome without conduction block, but with a serum IgM M-protein that bound to GM1 ganglioside. In this instance the association of the motor syndrome with an autoantibody directed against a neural antigen suggested that the disorder might be immune-mediated. However, attempts at immunosuppression had no effect on the progressive disease in that patient. A clinical response to immunotherapy remains a "gold standard", without which it is difficult to argue that a syndrome is immune mediated. In 1988 two patients with a multifocal motor neuropathy, motor conduction block, and serum IgM anti-GM1 antibodies were reported to improve after treatment with cyclophosphamide . It now appears that either motor conduction block or serum anti-GM1 antibodies alone can be markers for patients with LMN syndromes that often improve after immunomodulating therapy.
 

Multifocal motor neuropathy (MMN) and motor syndromes with serum anti-GM1 antibodies.

A. Clinical Syndromes

The immune-mediated motor neuropathies are characterized by asymmetric, slowly progressive weakness that most commonly begins in the arms. The age of onset is generally between 20 and 75. Men are affected somewhat more commonly than women. Motor findings include asymmetric weakness and variable degrees of atrophy. Patients with prominent conduction block may present with weakness in muscles with relatively normal bulk. Rarely, patients have had cranial nerve signs including external ophthalmoplegia and unilateral tongue weakness and atrophy. Some patients report paresthesias, but sensory signs are usually absent or clinically insignificant. In regions with normal strength tendon reflexes are often preserved. In areas of weakness, reflexes may initially be normal but can become reduced with progression of the disease. Fasciculations are not uncommon, and may add to diagnostic confusion between MMN and variants of amyotrophic lateral sclerosis (ALS) with only lower motor neuron signs. However, hyperreflexia and spasticity typical of ALS never occur in MMN.

B. Electrodiagnostic Classification