Clinical Features

Onset may be abrupt or insidious. Some pts have symptoms that are so trivial that they may not seek medical attention for months or years. Recurrent attacks of focal neurologic dysfunction lasting weeks or months and followed by variable recovery are typical; some pts initially present with slowly progressive deterioration. Symptoms often transiently worsen with fatigue, stress, exercise, or heat. Manifestations include weakness and/or sensory symptoms, visual difficulties, abnormalities of gait and coordination, urinary urgency or frequency, and fatigue. Motor involvement can present as a heavy, stiff, weak, or clumsy limb. Localized tingling, “pins and needles,” and “dead” sensations are common. Optic neuritis produces monocular blurring of vision, especially in the central visual field, often with associated retro-orbital pain accentuated by eye movement. Involvement of the brainstem may result in diplopia, nystagmus, vertigo, or facial pain, numbness, weakness, hemispasm, or myokymia (rippling muscular contractions). Ataxia, tremor, and dysarthria may reflect disease of cerebellar pathways. Lhermitte's symptom, a momentary electric shock-like sensation evoked by neck flexion, indicates disease in the cervical spinal cord. Diagnostic criteria are listed in Table 192-1 Diagnostic Criteria for Multiple Sclerosis (MS); MS mimics are summarized in Table 192-2 Disorders That Can Mimic Multiple Sclerosis (MS).

Physical Examination

Abnormal signs usually more widespread than expected from the history. Check for abnormalities in visual fields, loss of visual acuity, disturbed color perception, optic pallor or papillitis, afferent pupillary defect (paradoxical dilation to direct light following constriction to consensual light), nystagmus, internuclear ophthalmoplegia (slowness or loss of adduction in one eye with nystagmus in the abducting eye on lateral gaze), facial numbness or weakness, dysarthria, weakness and spasticity, hyperreflexia, ankle clonus, upgoing toes, ataxia, sensory abnormalities.

Disease Course

Three major subtypes:

• Relapsing MS (RMS) is characterized by discrete attacks of neurologic dysfunction over days to weeks with or without recovery; between attacks, no progression of neurologic impairment is noted. Accounts for 90% of new-onset MS cases.
• Secondary progressive MS (SPMS) always begins as RMS. At some point, however, the clinical course changes so that the pt experiences deterioration in function unassociated with acute attacks. SPMS produces more fixed neurologic disability than RMS. For a pt with RMS, risk of developing SPMS is ∼1-2% each year.
• Primary progressive MS (PPMS) accounts for ∼10% of cases. These pts experience a steady decline in function from disease onset. Compared to RMS, the sex distribution is more even, the disease begins later in life (mean age ∼40 years), and disability develops faster. Despite these differences, PPMS appears to represent the same underlying illness as RMS.

Progressive MS and Disease Activity. Pts with SPMS or even PPMS will occasionally experience relapses, albeit less often than in RMS. Progressive MS pts experiencing relapses or who are found to have acute new lesions on MRI are considered to have “active” MS. In contrast, the term “progression” is reserved to describe neurological worsening that accumulates independently from disease activity.

Most pts ultimately develop progressive neurologic disability. In older studies, 15 years after onset, only 20% of pts had no functional limitation, and between one-third and one-half of RMS pts progressed to SPMS and required assistance with ambulation. The long-term prognosis for MS has improved greatly in recent years due, at least in part, to widespread use of therapies for RMS.

Laboratory Evaluation

MRI reveals multifocal bright areas on T2-weighted sequences in >95% of pts, often in periventricular location; gadolinium enhancement indicates acute lesions with disruption of blood-brain barrier (Fig. 192-1. MRI Findings in MS). MRI is also useful to exclude MS mimics, although findings in MS are not completely specific for the disorder. CSF findings include mild lymphocytic pleocytosis (5-75 cells in 25%), oligoclonal bands (>75% have two or more), elevated IgG (80%), and normal total protein level. Visual, auditory, and somatosensory evoked response tests can identify lesions that are clinically silent; one or more evoked response tests are prolonged in 80-90% of pts. Urodynamic studies aid in management of bladder symptoms.

Therapies For Relapsing Forms of MS (Rms, Spms With Exacerbations)

More than a dozen are available.

Therapies For Acute Relapses

• Acute relapses that produce functional impairment may be treated with a short course of IV methylprednisolone (500-1000 mg IV q A.M. × 3-5 days) followed often by oral prednisone (60 mg q A.M. × 4, 40 mg q A.M. × 4, 20 mg q A.M. × 3). This regimen modestly reduces the severity and shortens the duration of attacks.
• Plasma exchange (seven exchanges: 40-60 mL/kg, every other day for 14 days) may benefit pts with fulminant attacks of demyelination (not only MS) that are unresponsive to glucocorticoids; cost is high and conclusive evidence of efficacy is lacking.

Therapies For Progressive MS

Symptomatic Therapy

• Spasticity may respond to physical therapy, baclofen (20-120 mg/d), diazepam (2-40 mg/d), tizanidine (8-32 mg/d), dantrolene (25-400 mg/d), and cyclobenzaprine hydrochloride (10-60 mg/d).
• Weakness can sometimes be improved with the use of potassium channel blockers such as extended release 4-aminopyridine (10 mg twice daily), particularly when lower extremity weakness interferes with the pt's ability to ambulate.
• Dysesthesia may respond to carbamazepine (100-1000 mg/d in divided doses), phenytoin (300-600 mg/d), gabapentin (300-3600 mg/d), pregabalin (50-300 mg/d), or amitriptyline (25-150 mg/d).
• Treatment of bladder symptoms is based on the underlying pathophysiology investigated with urodynamic testing: bladder hyperreflexia is treated with evening fluid restriction and frequent voiding; if this fails, anticholinergics such as oxybutynin (5-15 mg/d) may be tried; hyporeflexia is treated with the cholinergic drug bethanechol (30-150 mg a day), and dyssynergia due to loss of coordination between bladder wall and sphincter muscles is treated with anticholinergics and intermittent catheterization.
• Depression should be treated aggressively.

Variants of MS