Differential Diagnosisdisease Variants

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Prototypic MS is one of a spectrum of inflammatory demyelinating diseases. This includes acute MS (Marburg variant), Balo's concentric sclerosis, neuromyelitis optica (Devic's disease), and ADEM. Acute MS presents as a fulminant disease that causes severe disability shortly after onset and often death within 1 year. Lesions are more destructive than those of typical MS with axonal destruction and neurosis. Age of lesions is mixed, suggesting that disease is present prior to the clinical diagnosis. Balo's concentric sclerosis is another acute illness that has bands of demyelination alternating with preserved myelin areas. The cerebellum, brain stem, optic chiasm, and spinal cord are often spared. Devic's disease or neuromyelitis optica is defined by optic neuritis and myelopathy occurring together or within a short period of time. Pathologically, necrosis has been evident in both optic nerves and spinal cord, probably as a result of ischemia from swollen tissues.

ADEM is a polysymptomatic disease that occurs after upper respiratory infection or other viral infection or following immunization. The disease occurs more commonly in children than in adults and includes demyelination in multiple areas, including brain stem, spinal cord, optic nerves, cerebrum, and cerebellum. Patients may have associated febrile illness and can become comatose in rare cases. The percentage of patients that ultimately have a diagnosis of MS is low (i.e., 5%), but initial presentations, especially if not fulminant, can be confused with the first event of MS. Pathologically, there is infiltration of mononuclear cells with limited periventricular demyelination.

Other illnesses that present as a relapsing-remitting type of illness include Behcet's disease, characterized by oral or genital ulcerations, iridocyclitis, menin-goencephalitis, and thrombophlebitis. Lyme disease typically has radicular or peripheral nerve involvement but can be mistaken for MS because of its relapsing-remitting course and occasionally by its appearance on MRI. Sjogren's syndrome, in which individuals have vasculitis of the skin and peripheral nervous system associated with dry eyes and dry mouth, has also been confused with MS, in part because of MRI abnormalities that may mimic MS. Neurosarcoidosis may be a relapsing-remitting type of illness, but it generally has multiple cranial mononeuropathies. MRI shows lep-tomeningeal enhancement associated with intracranial disease. Cerebrovascular disease may be confused with MS, especially when interpreting MRI scans. Primary central nervous system vasculitis or systemic lupus erythematosus (SLE) may mimic the disease because of relapsing-remitting-type illnesses and white matter lesions present on MRI. The lesions seen with SLE tend to be subcortical and not periventricular. Vitamin B12 deficiency remains in the differential of MS; however, it tends to be a progressive-type disease with symmetric findings consistent with myelopathy and peripheral neuropathy. Myasthenia gravis may fluctuate in severity and could be confused with MS, especially when presenting with diplopia. Other bulbar features are uncommon in early MS, and lack of upper motor neuron findings can be helpful in distinguishing this illness. The hereditary dysmyelinating disorders are usually not confused with MS, although with adult onset of progressive myelopathy one must consider illnesses such as adrenolmyeloneuropathy.

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