Multiple Sclerosis

In MS, the initial attack occurs abruptly (minutes to hours) from a single lesion. These attacks last between 6 and 8 weeks. Recovery between bouts of demyelination can be incomplete or complete, depending on the amount of remyelination. Any part of the central nervous system can be affected. In decreasing order of frequency, the patient may exhibit optic neuritis, paresthesias in a limb, diplopia, trigeminal neuralgia, urinary retention, vertigo, or transverse myelitis. Depending on the spinal cord level, transverse myelitis can also cause loss of bladder or bowel function.

Ocular findings are the most common initial symptom. Optic neuritis is manifested as subacute monocular vision loss, although it can affect both eyes, and pain exacerbated with eye movement. It is the initial symptom in 25% and ultimately affects 50% of patients.¹ The course usually progresses over a period of 2 weeks and may be include headache, retroorbital or periocular pain, and alterations in color vision and visual fields. Slit-lamp examination may demonstrate cell and flare in the anterior chamber. The optic disk is frequently swollen on initial evaluation. In addition to optic neuritis, the patient may have an afferent pupillary defect (Marcus Gunn pupil, or decreased pupillary constriction on direct light confrontation but a normal consensual response) or intranuclear ophthalmoplegia, which is characterized by dysconjugate gaze with limited adduction of one eye and nystagmus in the abducting eye on lateral gaze as a result of a lesion involving the medial longitudinal fasciculus.

Sensory symptoms in patients with MS usually include numbness, tingling, pins and needles sensation, and tightness and coldness of the limbs and trunk. Radicular pain and itching may also occur. Symptoms result from involvement of the spinothalamic, posterior column, and dorsal nerve roots. The loss of vibration sense is often most prominent. Ataxia is uncommon at the onset of MS, but it occurs to some degree in most patients. Exacerbation of sensory symptoms can occur frequently and in different patterns with a patchy distribution. Patients may note either paresthesias or loss of sensation.

Sensitivity to heat is a characteristic complaint. Exercise, fever, a hot bath, or other activities that raise body temperature may result in the appearance of new symptoms or the recurrence of old symptoms. These events occur as a result of a temperature-induced conduction block across partially demyelinated fibers. Symptoms resolve when body temperature returns to normal.

In addition to loss of sensation, patients may also report “positive” symptoms. In addition to causing a slowing of conduction, demyelination may result in ectopic impulses with resultant abnormal signal transmission and abnormal mechanical sensitivity. These aberrant signals can produce the Lhermitte sign—an electric-like tingling or vibrating sensation in the torso or extremities with neck flexion. The patient may also report flashes of light (phosphenes) and paroxysmal symptom, including trigeminal neuralgia, ataxia, and dysarthria or painful tetanic posturing of the limbs triggered by touch or movement.

Motor weakness may occur in any pattern, including paraparesis, hemiparesis, and monoparesis; the lower extremities are usually affected more than the upper ones. Upper motor neuron dysfunction accompanied by spasticity and increased reflexes may also be present. Transverse myelitis with ascending weakness and numbness below the level of the lesion can occur as an initial symptom.

Autonomic symptoms are a frequent finding. Patients have difficulty with bladder function, including frequency and urgency, and may experience urge incontinence from bladder spasticity or hesitancy, retention, and overflow incontinence from poor signal conduction. Constipation is the most common bowel complaint. This autonomic dysfunction is frequently very embarrassing and distressful.

Normal disease progression is variable: MS may remain indolent or occur in a progressive manner, with steady accumulation of neurologic deficits in the absence of clearly defined exacerbations. Typically, acute exacerbations are followed by partial or complete resolution. New neurologic deficits develop over the course of several hours or days, remain stable for a few days to a few weeks, and then gradually improve.

With repeated exacerbations, permanent neurologic deficits tend to develop. Patients usually have symptom-free intervals of months or years between attacks. Patients who initially have relapsing-remitting disease (two or more episodes lasting more than 24 hours separated by more than 1 month) and who then enter a progressive phase are said to have secondary progressive disease (initial exacerbations and remissions followed by slow progression over at least a period of 6 months), whereas those whose symptoms are progressive from the onset are said to have primary progressive disease (slow or stepwise progression over a period of at least 6 months). About 15% of patients have primary progressive disease; of those who initially have relapsing-remitting disease, 30% to 50% will experience progressive symptoms during the first 10 years.

Optic Neuritis

Optic neuritis may occur by itself or be the initial symptom of MS. The relationship of optic neuritis to MS is controversial. Some regard optic neuritis as a distinct entity, but others consider it part of the clinical continuum of MS. More than half of all patients with MS have optic neuritis at some time during the disease. Patients with completely normal results on magnetic resonance imaging (MRI) and comprehensive cerebrospinal fluid (CSF) evaluation seldom progress to MS. Optic neurits is usually manifested initially as unilateral vision loss and retrobulbar pain with eye movement.

Transverse Myelitis

Like optic neuritis, transverse myelitis may occur in isolation or be part of the symptomatology of MS. It is usually manifested as paraparesis, which is initially flaccid and then spastic; as loss of sensation at a sensory level on the trunk; and as bowel and bladder dysfunction. Back pain precedes the neurologic symptoms, and the sensory symptoms may begin distally and ascend. The thoracic cord is most often affected.

Guillain-Barré Syndrome

Patients with GBS have weakness, paresthesias, and decreased or absent deep tendon reflexes. The distribution typically includes distal involvement with symmetric paresthesias (pins and needles). It spreads proximally, with weakness occurring a few days later; weakness also progresses to involve the upper extremities. Weakness is most prominent in the lower extremities and tends to involve the proximal muscles. It is usually first manifested as difficulty rising from a chair. The disease progresses from a few days to 3 to 4 weeks (progressive phase), followed by a plateau phase (days to weeks) and then by a recovery phase lasting from weeks to months. Weakness is varied but can be profound and involve the face and respiratory muscles. A loss or decrease in deep tendon reflexes is frequently the initial finding, and these reflexes should be tested if GBS is suspected. Variants include the acute axonal form, which has a poor prognosis, and the Miller-Fisher syndrome, which is characterized by ataxia, ophthalmoplegia, and areflexia.