Multiple Sclerosis

Multiple sclerosis is typically a chronic relapsing and remitting demyelinating disorder of the
central nervous system. The cause is unknown. Some patients develop a chronically
progressive form of the disease, either following a period of relapses and remissions
(secondary progressive) or, less commonly, from the outset (primary progressive).
Characteristically, the lesions occur at different times and in noncontiguous locations in the
nervous system—ie, "lesions are disseminated in time and space." Onset is usually in young
adult life; this disease rarely begins before 15 years or after 55 years of age. There is a
tendency to involve the optic nerves and chiasm, brainstem, cerebellar peduncles, and spinal
cord, although no part of the central nervous system is protected. The peripheral nervous
system is seldom involved.

Clinical Features

Optic neuritis may be the first manifestation. There may be recurrent episodes, and the other
eye usually becomes involved. The overall incidence of optic neuritis in multiple sclerosis is
90%, and the identification of symptomatic or subclinical optic nerve involvement is an
important diagnostic clue.

Diplopia is a common early symptom, due most frequently to internuclear ophthalmoplegia

that is frequently bilateral (Figure 14–12). Less common causes are lesions of the sixth or
third cranial nerve within the brainstem.

Nystagmus is a common early sign, and unlike most manifestations of the disease (which
tend toward remission), it is often permanent (70%).

Intraocular inflammation is associated with multiple sclerosis, particularly subclinical

peripheral retinal venous sheathing, which can be highlighted by fluorescein angiography.

In addition to ocular disturbances, there may be motor weakness with pyramidal signs, ataxia,
limb incoordination with intention tremor, dysarthria, urinary and/or bowel disturbance, and
sensory disturbance, particularly paresthesias.

Investigation

Diagnosis of multiple sclerosis traditionally relied upon clinical evidence of white matter
disease of the central nervous system disseminated in time and space (Schumacher criteria),
subsequently supported by MRI and cerebrospinal fluid abnormalities (Poser criteria).
Increasingly, emphasis is being placed on MRI abnormalities, in the brain and spinal cord,
supported by clinical features and cerebrospinal fluid abnormalities, to establish
dissemination in time and space (McDonald criteria), thus facilitating earlier diagnosis.

Cerebrospinal fluid oligoclonal bands that are not present in the serum—representing
intrathecal production of immunoglobulins—are characteristic but not diagnostic. There may
be cerebrospinal fluid lymphocytosis or a mildly raised cerebrospinal fluid protein
concentration during an acute relapse.

Retinal nerve fiber layer defects consistent with a subclinical optic neuritis can be detected in
68% of multiple sclerosis patients. The VER may help confirm involvement of the visual
pathway. It has been reported to be abnormal in 80% of definite, 43% of probable, and 22%
of suspected cases of multiple sclerosis.

Course, Treatment, & Prognosis

The course of disease is unpredictable. Optic neuritis rather than brainstem or spinal cord
disease as the initial manifestation is associated with a better prognosis. Relapses and
remissions are characteristic, permanent disability tending to increase with each relapse.
Pregnancy or the number of pregnancies has no effect on disability, but there is an increased
risk of relapse just after delivery. Onset during pregnancy has a more favorable outcome than
onset unrelated to pregnancy. Elevation of body temperature may exacerbate disability
(Uhthoff's phenomenon), particularly visual impairment.

Steroid treatment, usually oral or intravenous methylprednisolone, is useful in hastening

recovery from acute relapses but does not influence the final disability or the frequency of

subsequent relapses. Interferon and glatiramer acetate (copolymer 1) reduce the rate and
severity of relapses and slow the progression of brain MRI abnormalities. The effect on long-
term disability is still being determined. Many immunosuppressant treatments have been
tested for progressive disease with no significant benefit. Mitoxantrone, a chemotherapeutic
agent, and monoclonal antibody therapy have produce encouraging results for progressive
and recalcitrant relapsing-remitting disease.