On MRI, the lesions of lupus and of antiphospholipid antibody syndrome appear similar to plaques, and both the optic nerve (rarely) and the spinal cord may be involved, even repeatedly, in a succession of attacks resembling MS. The lesions may be small and single, multiple, or confluent in large regions (Akasbi). Nevertheless some of the lesions represent small zones of infarct necrosis rather than demyelination and are traceable to small-vessel occlusion. Other lesions may be inflammatory and demyelinating and these rheumatologic  processes that affect the cerebral white matter remain difficult to understand and it is these conditions that most closely simulate native MS. It is best for the moment to consider these as special manifestations of lupus or related diseases that mimic MS. The neurologist should be cautious in initiating some of the treatments for MS, such as β-interferon, as they may worsen the systemic autoimmune illness.
Periarteritis nodosa or vasculitis confined to the nervous system may produce multifocal lesions simulating MS. The distinction may be particularly difficult in rare instances of the vasculitic process in which the neurologic manifestations take the form of a relapsing or steroid-responsive myelitis. In these cases, the CSF may contain 100 or more white blood cells/mm3 and there may be no evidence of disease elsewhere in the nervous system. Occasionally, a young person with Lyme disease may have complaints of inordinate fatigue and vague neurologic symptoms coupled with hyperintense lesions on the T2-weighted cranial MRI. Close attention to the characteristic history (rash, arthritis, etc.) and serologic findings permit the distinction between MS and Lyme or other systemic diseases. The distinguishing features of Behçet disease are recurrent iridocyclitis and meningitis, mucous membrane ulcers of mouth and genitalia, and symptoms of articular, renal, lung, and multifocal cerebral disease. The chronic forms of brucellosis in the Mediterranean regions and Lyme borreliosis throughout North America and Europe may cause myelopathy or encephalopathy with multiple white matter lesions on imaging studies, but in each case the history and other features of the disease help to identify the infectious illness (see Chap. 31). Finally, a rare inflammatory variant of cerebral amyloid deposition can produce a few or a plethora of white matter lesions that superficially simulate MS but present with rapid dementia and TIA or stroke-like symptoms.
The purely spinal form of MS, presenting as a progressive spastic paraparesis, hemiparesis, or, in several of our cases, spastic monoparesis of a leg with varying degrees of posterior column involvement, is a special source of diagnostic difficulty. A tendency to affect older women has already been mentioned. Such patients require careful evaluation for the presence of spinal cord compression from neoplasm or cervical spondylosis. Dural arteriovenous fistula is also a consideration as mentioned below. Radicular pain at some point in the illness is a frequent manifestation of these disorders and is much less frequent in MS. Pain in the neck, restricted mobility of the cervical spine, and severe muscle wasting as a result of spinal root involvement, as is sometimes seen in spondylosis, are almost unknown in MS. However, atrophy of the first dorsal interosseus muscles, a frequent finding in spondylosis, also is seen in MS. As a general rule, loss of abdominal reflexes, erectile dysfunction, and disturbances of bladder function occur early in the course of demyelinating myelopathy but late or not at all in cervical spondylosis. The CSF protein in cervical spondylosis is often elevated, but oligoclonal bands and elevated IgG are not found.