Some patients who have only restricted bilateral signs of upper motor neuron disease prove to have multiple sclerosis, a slow compression of the spinal cord by spondylosis or meningioma, spinal dural arteriovenous fistula, or the myelopathic form of adrenoleukodystrophy (affected males or female carriers). In a few cases, tropical spastic paraplegia, HIV myelopathy, copper deficiency myelopathy, or a familial type of spastic paraplegia (described further on) will be uncovered. Exceptionally, progressive spastic paraparesis has been linked to an adult onset of phenylketonuria or other aminoacidopathies to vitamin B12 deficiency or to the fragile X premutation syndrome.
Diagnosis of ALS
The early clinical picture of motor system disease is closely simulated by a centrally placed cervical spondylotic bar or ruptured cervical disc, but with these conditions there is usually pain in the neck and shoulders, limitation of neck movements, and sensory changes, and the lower motor neuron changes are restricted to 1 or 2 spinal segments. The EMG is helpful, if not decisive, in differentiating these disorders. A mild hemiparesis or monoparesis because of multiple sclerosis may be, for a time, difficult to distinguish from early ALS and primary lateral sclerosis. Progressive spinal muscular atrophy may be differentiated from peroneal muscular atrophy (Charcot-Marie-Tooth neuropathy) by the lack of family history, the complete lack of sensory change, and different EMG patterns, as described in
Chap. 43. Motor system disease beginning in the proximal limb muscles may be misdiagnosed as an inflammatory myopathy or a limb-girdle type of muscular dystrophy.
The main considerations in relation to progressive bulbar palsy are myasthenia gravis and, less often, inflammatory myopathy, muscular dystrophy, and especially the inherited (Kennedy et al) type of bulbospinal atrophy, which is discussed further on. The spastic form of bulbar palsy may suggest the pseudobulbar palsy of lacunar disease and can be a prominent part of the progressive supranuclear palsy described earlier in the chapter. A crural form of PMA may be confused with diabetic polyradiculopathy or polymyositis.
A major consideration is the differentiation of PMA from a chronic motor polyneuropathy, particularly the form that displays multifocal conduction block. Extensive nerve conduction studies and EMG examinations are necessary to distinguish the two; these neuropathic processes are discussed with the peripheral neuropathies in Chap. 43. The presence of an IgM monoclonal paraproteinemia or of specific antibodies directed against the GM1 ganglioside are usually indicative of the immune motor neuropathy, but in half of the cases these laboratory tests are negative. There is also a rare form of subacute poliomyelitis (possibly viral) in patients with lymphoma or carcinoma; it leads to an amyotrophy that progresses to death over a period of several months. Chapter 30 discusses this paraneoplastic variety of motor system disease in greater detail.