Atypical and Inherited Motor Neuron Disorders

There are a heterogeneous group of motor neuron disorders that are rare but nonetheless important to recognize because they often mimic the presentation of amyotrophic lateral sclerosis (ALS). These often are referred to as atypical motor neuron disorders . They include several infectious, inflammatory (presumably autoimmune or paraneoplastic), traumatic, and structural etiologies. Although many of the atypical motor neuron disorders share some features with ALS, they often can be distinguished by their clinical and electrophysiologic characteristics ( Boxes 31.1 and 31.2 ). Others, including several familial forms of ALS (fALS) have an identical presentation to sporadic ALS. In these cases, only the family history and specific genetic analysis allow their differentiation.

One of the most important disorders that can be confused with motor neuron disease is the immune-mediated motor neuropathy multifocal motor neuropathy with conduction block (MMNCB). Strictly speaking, this is a disorder of the motor nerve and as such is discussed in detail in Chapter 29 . Patients present with progressive, asymmetric weakness and wasting that often affect the distal upper extremity muscles first. Weakness is in the distribution of named motor nerves, often with sparing of other nerves in the same myotome (clinical multifocal motor neuropathy). This pattern is not seen in ALS or its progressive muscular atrophy (PMA) variant, in which the entire myotome is characteristically affected at the same time. Occasional patients have weakness without wasting, a finding usually associated with pure demyelination. The disease is slowly progressive, with a male predilection, generally presenting before the fifth decade. Definite upper motor neuron signs are absent, although retained or inappropriately brisk reflexes for the degree of weakness and wasting may be seen. Bulbar function and sensation are characteristically spared. Mild or transient sensory symptoms may be present. The characteristic finding on motor nerve conduction studies is that of conduction block, temporal dispersion, or both along the motor nerves. Other signs of demyelination also may be seen, including slowed conduction velocities, absent or impersistent F responses, and prolonged distal motor latencies. Sensory conduction studies are typically normal. As noted earlier in Chapter 19 , neuromuscular ultrasound is quite useful in differentiating patients with MMNCB from a motor neuronopathy, such as the PMA variant of ALS. In the Goedee study, they determined that the optimal assessment was to inspect the bilateral median nerves in the forearms and upper arms combined with the bilateral trunks of the brachial plexus. When two or more nerve segments demonstrated enlarged nerves on ultrasound, the sensitivity of differentiating MMNCB from ALS was 68% with a specificity of 100%. A strong argument can be made for neuromuscular ultrasound screening of all patients with progressive lower motor neuron syndromes. As MMNCB is readily treatable, usually with excellent results, and PMA is a progressive, usually fatal neurodegenerative disease without any known treatment, it is essential to investigate the possibility of MMNCB as rigorously as possible.

Other than MMNCB, atypical motor neuron disorders are seen most often in association with certain viral infections or as the result of specific genetic mutations. Rarely, atypical motor neuron disorders are seen as a remote effect of some neoplasms or as a result of electrical injuries or radiation. Because the prognosis in ALS is so poor compared with these atypical motor neuron disorders, it is essential that the correct diagnosis is reached. In addition, some are potentially treatable; in others, genetic counseling is important.