The myelopathies discussed in this chapter have an underlying metabolic or toxic etiology. They have many clinical, electrophysiologic, and neuropathologic similarities. Preferential involvement of the dorsal columns and/or corticospinal tracts is commonly seen. Dorsal column involvement results in impaired position and/or vibration perception and sensory ataxia. Corticospinal tract involvement may lead to weakness, spasticity, hyperreflexia, extensor plantars, or sphincteric dysfunction. Variable degrees of peripheral nerve and/or optic nerve involvement may be present. In the presence of peripheral nerve involvement, the term myeloneuropathy is commonly used. A subacute symptom onset may be seen. Although therapy-related improvement may occur, a common outcome of therapeutic intervention is cessation of progression. Electrophysiologic studies may show evidence of central conduction delay, at times with variable peripheral nerve involvement. Pathologic studies may show involvement of the posterior columns, corticospinal tracts, and peripheral nerves in varying combinations.