MULTIPLE SCLEROSIS

Demyelinating diseases of the central nervous system (CNS) are characterized pathologically by an acquired loss of myelin with a relative preservation of axons. The most common and best known of the CNS demyelinating diseases is multiple sclerosis (MS). For many reasons, MS is also one of the most feared diagnoses in Neurology: it strikes young, healthy people in the prime of their lives; its course is marked by unpredictable relapses; almost any aspect of neurologic function may be affected; and some patients develop lifelong motor disability requiring a wheelchair.

MS has a wide range of presentations and an equally wide range of prognoses. Effective treatments aimed both at the underlying disease process and at some specific complications are available. For the student, the study of demyelinating diseases provides an excellent opportunity to learn about the dysfunction of different parts of the CNS and to master the wide variety of neurologic exam abnormalities that accompany these disorders.

Epidemiology

MS is a chronic neurologic disease that begins most commonly in young adulthood. The peak incidence of MS is between 20 and 30 years of age. Women are affected twice as often as men. MS prevalence in the United States is about 90 cases per 100,000 people. There are epidemiologic findings to suggest both genetic and environmental influences, as discussed below.

Geographically, MS is more common in northern latitudes. The incidence in Scandinavian countries is higher than that in southern Europe, and the incidence in the northern United States is higher than that in the South. There are racial differences as well, with a higher prevalence in white populations. Interestingly, those who move from a low-risk to a high-risk geographic region or vice versa before the age of 15 adopt the risk of MS associated with their new home, whereas those who migrate after age 15 retain the risk associated with their childhood home. The implications of this finding are unclear, but one theory is that a latent viral infection acquired in childhood may play a role in the pathogenesis of the disease.

There is strong evidence supporting a genetic predisposition to MS as well. For example, there is a greater incidence of MS in monozygotic, when compared with dizygotic, twins of patients with MS, as well as an increased incidence in association with particular human leukocyte antigen alleles.

Clinical Manifestations

Classically, MS is diagnosed by finding multiple white matter lesions separated in space and time. This means that multiple distinct areas of the CNS must be involved (rather than one area recurrently, for example), and that the disease must not be simply a monophasic illness (with multiple areas affected simultaneously but not recurring).

The clinical features are defined, as might be expected, by the location of the lesions. Thus, a right occipital lesion could result in a left homonymous hemianopia, whereas a right cervical spinal cord lesion may lead to an ipsilateral hemiparesis and loss of joint position sense, with contralateral loss of pain and temperature sensation. Almost any neurologic symptom, in fact, can be produced by an MS lesion.

Common clinical features (Table 20-1) include corticospinal tract signs such as weakness and spasticity, cerebellar problems such as intention tremor and ataxia, sensory abnormalities such as paresthesias and loss of vibration and proprioception sensation, and bladder dysfunction. Fatigue is a common complaint. In later stages, cognitive and behavioral abnormalities may occur. A few syndromes characteristic of MS warrant further description:

Optic neuritis (ON) is a common initial presenting symptom of MS. (This fact reminds us that the optic nerve is actually an extension of the CNS rather than a peripheral nerve.) ON is characterized by a mildly painful loss of visual acuity in one eye. The visual loss may range from mild blurriness with a loss of color discrimination to a severe episode with complete blindness. Pulling or tugging pain is most prominent when the eye moves. On examination, there is loss of acuity and color vision. Most patients have retrobulbar ON and the optic disc appears normal in the acute stage. In severe cases, however, the optic disc may be swollen, with indistinct margins (papilledema). A past history of ON is suggested by the presence of red desaturation (subtle loss of color appreciation), optic disc pallor or atrophy, and a relative afferent pupillary defect (RAPD, see Chapter 4).

Transverse myelitis is inflammatory demyelination in the spinal cord. Most commonly, this affects particular tracts at the level of the lesion in a patchy way, rather than producing complete involvement of the spinal cord. There may be unilateral or bilateral weakness or sensory loss below the lesion. Bowel and bladder function may be disrupted. Reflexes may be exaggerated below the lesion, and Babinski signs may be present. Patients may report a band of tingling or pain around the torso at the level of the lesion.

Internuclear ophthalmoplegia (INO) is a characteristic finding in MS. INO results from dysfunction of the medial longitudinal fasciculus and leads to an inability to adduct one eye when looking toward the opposite side, with associated nystagmus of the abducting eye. The adduction of both eyes when observing a near target (convergence) is preserved. The presence of INO in a young person suggests few other diagnostic possibilities. See Fig 4-2 for a more complete discussion of the pathophysiology of an INO.

The other clinical features characteristic of MS include Lhermitte’s sign, a tingling, electric sensation down the spine when the patient flexes the neck, and Uhthoff’s phenomenon, a worsening of symptoms and signs in the heat.

Clinical Course and Prognosis

Most MS patients begin with a relapsing-remitting course (Fig. 20-1), in which there are discrete episodes of neurologic dysfunction (relapses or “flares”) that resolve after several weeks or months. Unfortunately, such a course usually evolves into one in which recovery from each relapse is incomplete and baseline function deteriorates (secondary progressive). Rarely, patients may have a relentlessly progressive course from the onset, either with superimposed relapses (progressive-relapsing) or without (primary progressive).

FIGURE 20-1. Clinical course of multiple sclerosis: (A) relapsing-remitting, (B) secondary progressive, (C) primary progressive, (D) progressive-relapsing. (From Ginsberg L. Lecture Notes: Neurology. 8th ed. Oxford: Blackwell Publishing; 2005:131. Copyright © 2005 L Ginsberg. Reprinted by permission of John Wiley & Sons, Inc.)

To put the prognosis in broad terms, about 60% of MS patients lead lives of minimal disability and continue to work, about 20% require a walking aid but will remain ambulatory, and about 20% have severe disability, typically becoming wheelchair-bound. There has been and will likely continue to be a trend toward better prognoses in the future because of a greater use of effective disease-modifying agents. Features predicting a good prognosis include young age at onset, female sex, rapid remission of initial symptoms, mild relapses that leave little or no residual deficits, and a presentation with sensory symptoms or ON rather than motor symptoms.

Diagnostic Evaluation

The diagnosis of MS begins with a thorough history and examination. Patients often present with what appears to be a single episode of neurologic dysfunction, but upon further questioning recall earlier episodes of seemingly unrelated neurologic symptoms that may in fact represent prior lesions. It is important to inquire specifically about past neurologic symptoms that suggest ON, transverse myelitis, and other typical MS features. On examination, evidence of old optic nerve or other neurologic lesions should be sought.

The two most useful laboratory studies are magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis. On MRI, new MS lesions appear as discrete T2-hyperintense areas in the white matter of the brain or spinal cord (Figs. 20-2 and 20-3). Fluid-attenuated inversion recovery sequences also show these lesions particularly well. Acute lesions may not be evident on T1-weighted images but may enhance with gadolinium. Old, chronic MS lesions may become T1-hypointense, with a “black hole” appearance. MS lesions are most often ovoid in shape and have a predilection for particular areas, including the periventricular white matter, juxtacortical regions, corpus callosum, and cerebellar peduncles. Sagittal images may demonstrate foci of demyelination spreading perpendicularly from the corpus callosum, termed Dawson’s fingers.

FIGURE 20-2. T2-weighted MRI demonstrating multiple periventricular hyperdensities in both A and B (arrows), consistent with a diagnosis of MS. [MRI, magnetic resonance imaging; MS, multiple sclerosis.] (Reproduced with permission from Daffner RH. Clinical Radiology: The Essentials. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.)

FIGURE 20-3. T2-weighted MRI demonstrating a demyelinating plaque at the C3 level in the cervical spinal cord in a patient with MS. [MRI, magnetic resonance imaging; MS, multiple sclerosis.] (Reproduced with permission from Eisenberg RL. An Atlas of Differential Diagnosis. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2003.)

The characteristic CSF finding in MS is an elevation in the concentration of oligoclonal bands (OCBs), found in more than 90% of MS patients at some point during the illness. OCBs reflect intrathecal production of IgG antibodies by plasma cell clones. Although highly suggestive of MS, they can also be found in other neurologic disorders. CSF studies during an acute relapse may show a moderate pleocytosis and elevated protein. Calculation of the IgG index, on the basis of relative levels of IgG and albumin in the CSF and serum, can also suggest intrathecal antibody production.

Finally, visual evoked potentials can be used in suspected MS to document evidence of old ON. There is often an increased latency of the P100 wave on the affected side.

Related posts:

The Sensory System The Approach to Coma and Altered Consciousness Head Trauma Radiculopathy, Plexopathy, and Peripheral Neuropathy The Approach to Weakness Disorders of the Spinal Cord

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