MS is an immune-mediated disease, acquired by a genetically predisposed person near the time of puberty. Epidemiologic and pathologic aspects, as well as a host of immunologic factors, must be taken into account when considering the mechanism of demyelination. An immune-mediated inflammatory demyelination, probably genetically determined, may be the basis for the disease. Markers for immunopathologic processes, such as perivascular infiltration by lymphocytes, major histocompatibility complex antigen expression by cells in the lesions, lymphokines and cytokines secreted by activated cells, and absence of evidence of infection, are all involved in the pathogenesis (Korn, 2008; Rubin & Strayer, 2012).

Indicators support a possible autoimmune response for MS from microscopic appearance of lesions. CD4+ helper cells, CD8+ T cells, perivascular lymphocytes, and macrophages have been isolated in lesions in chronic MS. The CD4 + T cells isolated from cerebral spinal fluid (CSF) are oligoclonal. Currently no target antigen has been isolated; there seems to be a specific immune response to a central nervous system protein (Korn, 2008; Noseworthy et al., 2000; Rubin & Strayer, 2012).

DIAGNOSTIC CRITERIA

No specific test for MS exists. The evidence supporting diagnosis consists of multiple signs and symptoms and characteristic remissions and exacerbations and diagnostic testing results. MS is characterized by dissemination in time and space—in other words, there are multiple episodes of dysfunction and multiple areas of involvement within the CNS. Traditionally, the diagnosis usually was not made with assurance at the first attack.

There must be two separate or distinct episodes of neurological symptoms, each lasting 24 hours, separated by 1 month (separation of time) and involving different parts of the nervous system. There must be clinical evidence of two separate lesions (separation of space) on physical examination or clinical evidence of one and paraclinical evidence (neuroimaging, electrophysologic, and neuropsychiatric) of another. The final diagnostic criterion is that the patient’s signs and symptoms cannot be explained by another pathological process (Dumphy et al., 2011). The most recently updated 2010 McDonald criteria allow for a diagnosis after the first episode. According to the 2010 McDonald criteria, patients can be diagnosed if the clinical presentation contains two or more attacks with two or more objective clinical lesions; no further data are needed (Polman et al., 2010).

COURSE OF THE DISEASE

MS falls into one of four categories (Dumphy et al., 2011; Rubin & Strayer, 2012; Moses, Picone, & Smith, 2008; Wolinsky, 2005):

CLINICAL MANIFESTATIONS

As previously discussed, the hallmark symptom of MS is demyelination of the nerve fibers. Demyelination of the nerve fibers is responsible for an interruption in neural conduction resulting in a number of symptoms. Symptoms are based on the extent and location of the lesion or lesions. The initial symptoms may occur alone or in combination. The distribution of pathologic lesions accounts for the wide variety of symptoms. The clinical picture objectifies the loss, permanent or temporary, of normal impulse-conduction properties in myelinated nerve fibers. The fibers can be in the long ascending and descending tracts of the spinal cord, the shorter white-matter tracts within the brainstem, or the subcortical white matter of the cerebrum and cerebellum.

The areas most commonly affected by MS include motor, sensory, cerebellar, and emotional areas. Visual field deficits secondary to optic nerve involvement, as well as speech and swallowing difficulties, are secondary to corticobulbar tract involvement. Gait and coordination are impaired when lesions are in the cerebellar tracts. Muscle strength and balance are affected when lesions are located in the corticospinal tract and the spinocerebellar tract. Position sense and vibratory sensation are affected when the posterior cell columns of the spinal cord are demyelinated. Emotional or psychological manifestations can include mood swings, depression, and apathy.

Motor Symptoms

Pyramidal tract involvement produces characteristics of upper neuron disease: spasticity, hyperreflexia, clonus, and extensor plantar responses. Deep tendon reflexes are exaggerated, sustained clonus may be elicited (usually at the ankles), and extensor plantar responses may be observed. Commonly, these signs are asymmetric. Deep tendon reflexes can be decreased if they are interrupted by a lesion at a certain segmental level of the spinal cord. The Achilles reflex may be absent, and sphincter and sexual dysfunction may be present if lesions are found in sacral segments (Daroff, Fenichel, Jankovic, & Mazziatta, 2012)

Triceps jerks are lost more frequently in the upper extremities; ankle jerks are lost more frequently than knee jerks. In established disease in the upper limbs, biceps and supinator jerks may be associated with finger flexion and Hoffman’s sign. If the reflex is present, flicking or nipping the nail of the second, third, or fourth finger causes flexion of these fingers and possibly the thumb. Its presence indicates that the tendon reflexes are hyperactive. An increased jaw jerk suggests involvement above the level of the foramen magnum (Matthews, 2005).

Increased muscle tone is an important factor in this disease. In less-severe cases, there is spasticity of the extensor muscles of the legs. This occurs in bed at night or when trying to rise in the morning. The legs are held rigidly extended, usually for several minutes. These spasms are seldom painful but are inconvenient. As the disease progresses, the flexor muscles become spastic. The patient may fall without warning while walking. Flexor spasms are frequently painful (Matthews, 2005).

Bilateral involvement of the corticobulbar tracts occurs in some patients; this leads to dysarthria, dysphagia, hyperactive jaw jerks, bifacial paralysis, and apparent emotional lability. Spastic weakness of the muscles of speech is common. In the early stages, speech is often slurred. As the disease progresses, speech becomes explosive or staccato and unintelligible. Scanning speech—slow and measured speech with pauses between syllables—is seen in later stages of the disease (Hickey, 2013).

Sensory Symptoms

Sensory symptoms are the most common initial features of MS and occur throughout the course of the disease. These symptoms are varied and the onset may be symmetrical. The sensations are described as tingling, numbness, a pins-and-needles sensation, tightness, coldness, or swelling of the limbs or trunk. Complaints of tight bands or straps around the trunk or limbs are characteristic (Daroff et al., 2012). A common pattern is for unusual sensations to begin in one foot and spread to both lower limbs, the buttock, the perineum, and the trunk within a few days.

The normal sensation of micturition and defecation may be affected, but control remains normal. Vaginal sensation is also diminished. The examination may reveal no loss of light touch or pinprick, but the pinprick may feel distant, as if something is between the pin and the skin. An intensely itching pain, especially in the cervical dermatomes, usually unilateral and occurring in young women, is suggestive of MS (Daroff et al., 2012).

The most frequent sensory signs are varying degrees of impairment of vibration and joint position sense, decrease of pain and light touch in a stocking-and-glove distribution in the four extremities, and patchy areas of reduced pain and light-touch perception in the limbs and trunk (Daroff et al., 2012).

Lhermitte’s sign consists of an electric feeling passing down the back to the legs on flexing the neck. This is common in MS but can occur in other conditions (compressive myopathies). The usual course of a sensory episode is toward complete remission within 6 to 8 weeks; for patients who have frequent attacks, these episodes may clear in 10 days. Observant patients may recognize sensory symptoms of a more localized nature that last for only 1 to 2 days, unrelated to exercise, infection, or environmental temperatures (Matthews, 2005). Sensory symptoms tend to remit more frequently than do symptoms involving other systems.

Cerebellar Involvement

Cerebellar dysfunction is characterized by gait imbalances, difficulty in performing coordinated actions with the arms, and slurred speech. Cerebellar signs are usually uncommon at the onset of the disease (Matthews, 2005). The early appearance of cerebellar ataxia is an indication of a poor prognosis, and cerebellar signs often persist. There may be difficulty in distinguishing cerebellar signs from those of weakness, spasticity, sensory loss, and vertigo. Cerebellar ataxia naturally affects the gait, but spasticity and weakness are more important causes of disability.

Conventional heel–knee shin tests are poorly performed by weak and spastic legs. Truncal ataxia and gait are not obvious when sitting but contribute to poor balance. These abnormalities may be observed by having the patient stand or walk normally. Cerebellar incoordination in the upper limbs may be terribly disabling, especially when combined with any significant degree of intentional tremor. Severe degrees of intentional tremor may render the hands useless; voluntary movement can be disturbed by violent deviations of the arms that may render the patient unapproachable (Matthews, 2005).

Visual Involvement/Optic Neuritis

Many patients with MS display abnormalities of vision. These defects are the result of lesions of the optic nerve or chiasm. Even patients who do not demonstrate a clinically detectable visual defect often do so electrophysiologically through the measurement of visual evoked potentials. Evoked potentials are considered extensions of the clinical examination and allow objective measurement of lesions in specific pathways (Calabresi, 2012).

Pain most commonly precedes the onset of visual symptoms but can occur simultaneously with the onset or develop subsequently. The pain is felt in the eye or is supraorbital and is often accompanied by unilateral or generalized headaches. Tenderness may be elicited by putting pressure on the globe. The pain varies in intensity. It can be aggravated by movement of the eye or may be present only on movement. Absence of pain does not exclude the diagnosis, nor does the severity of pain represent a poor prognosis. Treatment with steroids or adreno-corticotropic hormone (ACTH) often relieves the pain. The period from the onset of visual symptoms to peak loss of acuity is usually 3 to 7 days (Matthews, 2005).

In mild cases, where the lesion is retrobulbar, the optic disc may appear normal. In more severe cases, the disc shows indistinct margins and may be pinker during the acute stages. There may be edema or slight swelling of the disc. If there have been previous attacks of optic neuritis, pallor of the disc can progress to the chalk white of optic atrophy (Eze et al., 2013; Guercio & Balcer, 2008).

In many of cases, there is some degree of pupillary dilation. The Marcus Gunn pupillary response, also known as afferent pupillary defect, is noted in these patients. When light is shined in the normal eye, bilateral pupillary constriction results. Shining the light into the diseased eye, however, produces delayed or incomplete direct pupillary constriction. If the light is moved from the unaffected eye to the abnormal eye, the pupil appears to dilate on illumination (Bickley & Hoekelman, 2013). The visual field defect in most patients is either a central scotoma or generalized impairment of the whole field (Matthews, 2005).

Recovery of visual acuity is the rule after an initial attack of optic neuritis, although there are exceptions. Optimal acuity is achieved after a mean of 2 months from onset. Improvement can continue, but at a decelerating rate. Recovery of normal vision does not mean full recovery of function of the optic nerve or complete freedom from symptoms. There may be a slight dulling of visual images and lack of appreciation of brightness of colors (Matthews, 2005).

Brainstem Functions

Demyelination of the third, fourth, and sixth cranial nerves before they leave the brainstem is the cause of diplopia. Diplopia may also occur as a result of demyelination of the medial longitudinal bundle, which links the third, fourth, and sixth nuclei (Eze et al., 2013; Guercio & Balcer, 2008). Characteristic of such a lesion is internuclear ophthalmoplegia (weakness of adduction with nystagmus of the abducting eye on lateral gaze) (Eze et al., 2013; Guercio & Balcer, 2008).

Nystagmus occurs in the majority of MS patients. Different forms of nystagmus occur. Horizontal nystagmus on lateral gaze is most common. Jelly nystagmus can be detected only when inspecting the fundus with an ophthalmoscope; the optic disc can be seen to jerk rapidly from side to side over a small range (Matthews, 2005).

Facial numbness may accompany symptoms of sensory relapse. The lack of pain and preservation of taste distinguish it from Bell’s palsy. Facial myokymia occurs in MS and also in other conditions (e.g., Guillain–Barré, posterior fossa tumors, pontine glioma). The onset is sudden: The patient complains of stiffness of the face that makes certain movements difficult, even though there is no weakness or pain. Patients may observe their own reflections and see that the face is drawn up on the affected side; the palpebral fissure is slightly narrowed and the nasolabial fold deepened. Slight contraction of all the muscles on one side of the face is accompanied by an extraordinary rapid flickering that passes over the face in undulating waves. Remission occurs within 1 week to 6 months (Matthews, 2005).

Vertigo occurs as an initial symptom in a small percentage of cases. It is usually of acute onset and is prostrating. When the patient lies perfectly still, it subsides, but any movement of the head immediately aggravates it. Nystagmus is seen and increased with head movement. The duration of the attack is variable, from a few days to several weeks. During the course of the disease, vertigo occurs in many of the patients, usually accompanied by vomiting. Demyelination may occur in the olfactory and auditory nerves, the only other cranial nerves in which oligodendro-glial cells are present.

Autonomic Nervous System

BLADDER

Loss of bladder control is the most important autonomic disturbance to MS patients. Isolated instances of retention or incontinence may be realized in retrospect as the first evidence of the disease. When evaluating bladder incontinence or urgency, the provider must rule out other causes of these problems. Usually there is urgency of micturition in mild relapses involving the spinal cord. If there is a remission, bladder function is restored, but if a mild motor disability persists, urgency continues (Matthews, 2005).

Small quantities of urine are passed with urgency accompanied by hesitancy. Frequency also is a problem with increasing disability. The nature of the urgency changes and large quantities of urine are passed without warning, without sensation, leading to a state of constant dribbling. Acute retention can occur at any stage of the disease but usually resolves. Recurrence is common. The degree of bladder disorder is usually related to the severity of motor and sensory impairment, but there are exceptions (Calabresi, 2005). Urinary infections are common in MS patients, especially in women. They do not usually cause fever and back pain but present as an increase in bladder or neurologic dysfunction (Daroff et al., 2012).

Fecal incontinence is uncommon. As the disease advances, constipation becomes a major manifestation, reflecting upper and lower motor neuron impairment in addition to decreased general mobility (Daroff et al., 2012). Patients with paraplegia usually need a bowel regimen to maintain regular bowel movements.

Sexual Function

Sexual dysfunction can affect the quality of life in MS patients, who are usually of childbearing age (Mattson, 1995). Disorders of sexual function are common. Among the commonly reported problems in men were erectile dysfunction, trouble achieving orgasm, and inability to ejaculate. Women reported decreased vaginal lubrication, trouble achieving orgasm, and decreased vaginal sensation. Patients who began receiving steroids for nonsexual exacerbation had a lower incidence of sexual dysfunction. There was no relationship among the presence of sexual dysfunction and age, duration of disease, type of disease, or degree of disability.

Issues of sexual function should be an important consideration in the care of these patients. Although impotence is usually associated with prolonged disease, it can occur in the first episode. There is a clear relationship between impotence and sphincter disturbance and also the duration of the disease. In men who were totally impotent, sweating was absent below the waist; in partial impotence, sweating was absent below the groin (Matthews, 2005).

Cortical Function

Depression in MS patients is probably not caused by the disease process; instead, it is a reaction to the prospect of chronic progressive disability and isolation (Matthews, 2005). Pathologic laughing and weeping are extreme examples of lability of affective display. The patient cannot modulate affective expression, so even mild emotional stimuli bring on an emotional display that is exaggerated in its intensity. These displays are socially disabling and are likely to disrupt personal relationships. Emotional communication can be disrupted because facial expression may not reflect what the patient is saying. While patients are laughing, it is hard to recognize depression or to appreciate that they are feeling bad (King & Reiss, 2013; Paparrigopoulos, Ferentinos, Kouzoupis, Koutsis, & Papadimitriou, 2010).

Seizures

Seizures appear on every list of symptoms at the onset or during the course of the disease. Tonic–clonic or partial motor seizures occur in a small percentage of MS patients. Demyelinating disease is the cause in some patients; however, MS patients can also be affected by other disorders of the CNS, so it is important to determine the etiology of seizures (Matthews, 2005).

DIAGNOSTIC STUDIES