Multiple sclerosis II

Differential diagnosis

The diagnosis of MS depends on identification of multiple episodes of demyelination separated in space and time. The occurrence of a single episode does not lead to a diagnosis of MS. The differential diagnosis for the most characteristic episodes will be considered individually. The differential diagnosis of multiple episodes will then be considered.

Single episodes

Optic neuritis

The most important differential is with optic nerve compression. This is usually more insidious in onset and is progressive. This can be ruled out by MRI scan. Between 25 and 60% of patients first presenting with optic neuritis go on to develop MS.

Spinal cord syndromes

The most important differential diagnosis is spinal cord compression (Fig. 1a). In more insidious spinal cord syndromes, the differential diagnosis includes rarer spinal cord disease such as vitamin B12 deficiency, HTLV-1 myelopathy and familial spastic paraparesis. In patients lacking sensory signs, consider amyotrophic lateral sclerosis; associated lower motor neurone signs allow a distinction. After first presentation with complete transverse myelitis, patients later develop MS; those with partial spinal cord syndromes more often progress (70%).

Fig. 1 MRI in multiple sclerosis. (a) A T2-weighted scan of the cervical spine showing intrinsic high-signal changes; (b) a proton-weighted axial scale scan showing periventricular high-signal changes.

Brain stem syndromes

The differential diagnosis is wide, including tumours, brain stem encephalitis, cranial polyneuritis, an Arnold–Chiari malformation or vascular disease, the last being the most common alternative in older patients. MRI may clarify this differential; CSF examination and other investigations may be needed.

Multifocal CNS disease

The relapsing remitting form of MS can be mimicked by other inflammatory diseases such as systemic lupus erythematosus, sarcoid, Behçet’s disease and polyarteritis nodosa, and infectious diseases such as Lyme disease and syphilis. These are all rare. A monophasic illness characterized by widespread multifocal demyelination can occur either in isolation (acute disseminated encephalomyelitis) or after an infection (post-infectious encephalomyelitis). In these conditions, there are multiple areas of demyelination separated in space but not in time.

Investigations

The investigation of a patient with suspected MS can be divided into:

excluding other causes for the clinical syndrome

finding abnormalities characteristic of MS.

Excluding other causes

Some of the most common presentations and their investigations are discussed above. The investigation of any first presentation is more intensive than the investigation of a relapse. However, even patients with an established diagnosis of MS can develop unrelated neurological complications.

Finding characteristic abnormalities

Demonstrating clinically silent lesions

MRI is particularly powerful at detecting clinically silent lesions in MS. These tend to occur in characteristic sites within the white matter: the periventricular region and corpus callosum (see Fig. 1). Similar changes can be seen in the spinal cord, though these are more commonly found when symptomatic. If a scan is enhanced with gadolinium, then active lesions can be seen; the enhancement persists for 6–8 weeks.

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