|
| A) | near the equator. | ||
| B) | in the extreme north. | ||
| C) | in the extreme south. | ||
| D) | in developed countries. |
Environmental factors are thought to play a significant role in the development of MS. Studies have shown an association between geographic latitude and risk, with the risk increasing from south to north [16,17]. The lowest risk in found among persons living near the equator. As such, the prevalence of MS is higher in geographic locales having less sunlight exposure (and hence diminished production of vitamin D), suggesting that low levels of vitamin D may be a risk factor [17,18,19,20]. In addition, persons who smoke have an increased relative risk compared to those who do not [17,19,21].
| A) | occur only in the brain. | ||
| B) | cluster near the ventricles. | ||
| C) | cluster in the peripheral nerves. | ||
| D) | occur primarily in the gray matter. |
Conceptually, MS is now considered to be an autoimmune inflammatory disorder with complex and variable pathologic features [1,29]. Susceptible individuals are those of genetic predisposition in combination with environmental factors and possibly latent infection. The etiology is unclear, but initiation of disease appears to involve the activation of peripheral T-lymphocytes, programmed to recognize components of the CNS axonal myelin sheath. The disease is triggered by events that permit these autoactivated T-cells to breach the blood-brain barrier and cross-react with myelin components within the white matter of the brain and spinal cord [30]. This precipitates a cascade of immune-mediated inflammatory tissue injury. As seen on radiographic imaging and pathologic examination, the hallmark of the disease is this well-defined, focal zone of injury ("plaque") containing elements of inflammation, demyelination, and axon degeneration [1,6]. Such lesions may be single or multiple, and over time, they may be partially reparative, relapsing, or recurrent in new locations. The location of lesions is variable; early in the disease they appear in white matter, often clustering near the ventricles and sparing peripheral nerves [14].
| A) | impairs nerve transmission. | ||
| B) | bolsters the immune attack on oligodendrocytes. | ||
| C) | causes perpetuation of the proinflammatory condition. | ||
| D) | permits leukocytes to enter the central nervous system (CNS). |
Demyelination impairs nerve impulse transmission and leads to abnormal patterns of nerve conduction, which accounts in large part for the various clinical symptoms and signs of MS. Oligodendrocytes are cells that elaborate the myelin sheath that envelops the axon. During the early, remittent stage of the disease, as inflammation subsides, the number and function of these cells are sufficient to renew the myelin sheath (remyelination) and restore neurologic function. Over time, the repeated inflammatory insults associated with relapsing MS lead to a gradual depletion of functioning oligodendrocytes, and to degenerative changes marked by central scarring within the lesion and focal areas of cerebral atrophy. The clinical correlate is the gradual accumulation of fixed neurologic deficits as the patient with MS transitions to the chronic progressive stage of the disease.
| A) | is never painful. | ||
| B) | does not usually affect ambulation. | ||
| C) | usually affects the muscles of the trunk and face. | ||
| D) | is more prominent in the lower extremities than the upper extremities. |
The majority of patients with MS report some level of spasticity. Painful muscle spasm is experienced by approximately 15% and is often a source of debilitation [39]. Spasticity usually affects the muscles of the extremities (more prominent in the lower extremities than the upper extremities) and can impair an individual's ability to freely move his or her muscles.
| A) | visceral. | ||
| B) | somatic. | ||
| C) | neuropathic. | ||
| D) | musculoskeletal. |
MS pain is mainly neuropathic—the result of nerve damage and faulty conduction—and can include stabbing, burning, and shock-like sensations (e.g., allodynia, dysesthesias, paresthesia). Lhermitte sign is often considered a classic sign of MS and consists of a brief, electric shock-like sensation that runs down the spine and is triggered by bending the neck forward or backward.
| A) | astigmatism. | ||
| B) | optic neuritis. | ||
| C) | upbeat nystagmus. | ||
| D) | intranuclear ophthalmoplegia. |
Impaired vision is frequently present in patients with MS, most commonly unilateral optic neuritis, which is present in approximately in 66% of cases [43]. Optic neuritis usually manifests as acute or subacute unilateral eye pain that increases with eye movements [44]. It can also lead to blurring or graying of vision or blindness in one eye. However, while unilateral optic neuritis is common in MS, simultaneous bilateral optic neuritis (resulting in total blindness) is rare [43]. Approximately 90% of patients with MS regain normal vision over a period of two to six months after an acute episode of optic neuritis [43].
| A) | benign. | ||
| B) | malignant. | ||
| C) | relapsing-remitting. | ||
| D) | primary progressive. |
Relapsing-remitting multiple sclerosis (RRMS) is characterized by alternating series of clearly defined clinical relapses (or exacerbations) followed by periods of partial or complete recovery (remissions). RRMS affects young adults, is three times more common in women than men, and accounts for about 85% of all cases of MS [51]. Functional and structural impairments suffered during relapses may either resolve or leave sequelae.
| A) | alternating series of clearly defined relapses followed by remissions. | ||
| B) | steady disease progression with occasional remissions and temporary minor improvements. | ||
| C) | a long-term absence of symptoms with no functional impairments 15 years after disease onset. | ||
| D) | progressive neurologic impairment between relapses without any well-defined periods of remission. |
Primary progressive MS (PPMS) is characterized by steady disease progression from the onset of symptoms, perhaps with occasional remissions and temporary minor improvements [47]. Approximately 10% to 15% of patients with MS carry the diagnosis of PPMS [49]. Patients diagnosed with PPMS tend to be older (mean age: 40 years) than those with RRMS, and there is no gender difference in incidence [49].
| A) | occurs most commonly in older adults. | ||
| B) | is also known as Uhthoff phenomenon. | ||
| C) | is associated with smaller lesions involving the cervical spine. | ||
| D) | results in major disability and usually death within one year of onset. |
Malignant MS (also known as Marburg variant) is characterized by a rapidly progressive course resulting in major disability and usually death within one year of the onset. This disease course is most common in children, although older adults may be affected as well.
| A) | accounts for the majority of MS cases. | ||
| B) | is usually characterized by a relapsing-remitting course. | ||
| C) | is only diagnosed in patients younger than 10 years of age. | ||
| D) | most commonly presents with motor, rather than sensory, symptoms. |
Early-onset MS is usually diagnosed in patients younger than 20 years of age. It accounts for approximately 0.4% to 10.5% of all MS cases [56]. Usually, the disease is characterized by a relapsing-remitting course, a high recovery rate from initial attack, and a long remission and slow progression rate. Sensory symptoms are more common than motor symptoms in these patients, and vision loss (optic neuritis) is a common initial presentation. Other functional systems are involved with a variable frequency. Seizures, malaise, irritability, and low-grade fever may also be present.
| A) | optic neuritis. | ||
| B) | loss of proprioception. | ||
| C) | lesions on the cervical spine. | ||
| D) | peripheral vestibular disease. |
NEUROLOGIC SIGNS AND TESTS
| Test | Description | Notes |
|---|---|---|
| Romberg test | Patient stands erect with feet together and eyes closed. Swaying or falling is considered positive. | Used for patients with ataxia. Indicates loss of proprioception. |
| Lhermitte sign | Patient bends the head forward or clinician puts pressure on the posterior cervical spine. An electrical shock sensation is considered positive. | Used to determine the presence of lesions on the cervical spine. Often considered a classic finding in MS but can be caused by a number of conditions. |
| Gait tests | Observe patient walking normally, walking heel-to-toe, and walking on only toes/heels. Any abnormalities should be noted. | This test evaluates ataxia in various parts of the body. |
| Point-to-point movement evaluation | Patients alternate touching their extended index finger to their nose and the examiner's outstretched finger. | These are tests to evaluate ataxia, dysmetria, and cerebellar dysfunction. Positive findings are indicative of loss of motor strength, loss of proprioception, or a cerebellar lesion. |
| Supine patient places right heel on left shin just below the knee and slides it down to the top of the foot as quickly as possible without making mistakes. Repeat on opposite side. Inability to complete quickly is considered positive. | ||
| Visual acuity and color tests | Patient reads letters from a board to assess visual acuity and from the Ishihara Color Vision Test to assess color vision. Inability to distinguish figures is considered positive. | These tests evaluate for the presence of optic neuritis, perhaps the most frequent symptom in MS. |
| Babinski sign | The lateral side of the sole of the foot is lightly stimulated from the heel along a curve to the toes. If the hallux dorsiflexes and the other toes fan out, this is considered a positive Babinski sign. | These tests evaluate for signs of disease process in the motor neurons of the pyramidal tract. They are positive in individuals with neurologic problems of the corticospinal tract, including those with MS. |
| Chaddock sign | Similar to Babinski's sign, this test involves stimulation over the lateral malleolus rather than the bottom of the foot. A positive response elicits an extensor response similar to Babinski sign. | |
| Hoffman reflex | Clinician taps the nail or flicks the terminal phalanx of the middle or ring finger. A positive response is seen with flexion of the terminal phalanx of the thumb. | This test evaluates problems in the corticospinal tract. However, it is also positive in hyper-reflexive patients. Findings that are acute or asymmetrical are more indicative of disease. |
| Halmagyi-Curthoys head impulse test | Clinician randomly moves the patient's head side to side. If the eyes remain stationary while the head is moved, this is considered positive. | Test reveals dissociation between movement of the eyes and of the head. Indicative of peripheral vestibular disease. |
| Perception tests | A monofilament, tuning fork, or pin is applied to patient's body. Ability to perceive the touch or vibration is considered positive. | Evaluates the level of sensory perception in certain parts of the body. |
| Muscle strength tests | Patient attempts to resist pressure applied by the clinician to various muscle groups. Level of resistance can be rated on a scale from none to normal strength. | Patterns of weakness can help localize a lesion to a particular cortical or white matter region, spinal cord level, nerve root, peripheral nerve, or muscle. Differences in strength between left and right sides are easier to evaluate than symmetrical loss unless the weakness is severe. |
| Reflexes | This is done with both ends of the hammer. The reflexes can be normal, brisk (i.e., too easily evoked), or non-existent. | — |
| A) | central cord. | ||
| B) | dorsal columns. | ||
| C) | lateral corticospinal tract. | ||
| D) | lateral spinothalamic tract. |
MS lesions found in the spinal cord usually give rise to identifiable symptoms and are highly eloquent of the disease process; new spinal MS lesions are strongly correlated to new clinical manifestations. Approximately 75% of patients with MS have lesions within the spinal cord, principally the cervical cord, and most spinal cord lesions are located in the dorsal columns [68]. These lesions are usually oval or cigar-shaped and can span one or two vertebral segments (referred to as skip lesions).
| A) | Progressive from onset | ||
| B) | Lack of peripheral symptoms | ||
| C) | Abnormal neurologic examination | ||
| D) | MRI abnormalities in multiple locations |
Atypical clinical features that suggest an alternate diagnosis include [96]:
Normal neurologic examination
Abnormality in a single location (i.e., no dissemination in space)
Progressive from onset (i.e., no dissemination in time)
Onset in childhood or at an age older than 50 years
Psychiatric disease present
Systemic disease present
Prominent family history (may suggest genetic disease)
Gray matter symptoms (e.g., dementia, seizures, aphasia)
Peripheral symptoms (e.g., peripheral neuropathy, fasciculations)
Acute hemiparesis
Lack of typical symptoms (e.g., no optic neuritis, bladder problems, Lhermitte sign)
Prolonged benign course (i.e., diagnosis made several years ago with few current findings)
| A) | interferons. | ||
| B) | corticosteroids. | ||
| C) | adrenocorticotropic hormone (ACTH). | ||
| D) | Both B and C |
Treatment of the acute exacerbations seen with relapsing types of MS relies primarily on corticosteroids and adrenocorticotropic hormone (ACTH). These agents have been found to promote speedier resolution of the neurologic deficits, lessen the severity of an attack, and effectively reduce the risk of permanent residual deficits. Both corticosteroids and ACTH are capable of restoring the breakdown of the blood-brain barrier, reducing inflammation, and immunomodulating mononuclear trafficking mechanisms. Corticosteroids also promote quick recovery from disability [98,99].
| A) | 80–120 units ACTH for one to three weeks. | ||
| B) | IV methylprednisolone (1 g) for five to seven days. | ||
| C) | 44 mcg ß-interferon subcutaneously three times per week. | ||
| D) | 500–1,250 mg oral prednisone daily divided for three to seven days. |
The first-line treatment of MS-related exacerbations involves administration of high doses of IV corticosteroids, usually methylprednisolone (1 g daily), for five to seven days [100,101]. Alternative approaches for patients who do not tolerate large intravenous dosage or have poor venous access include:
Repository ACTH (corticotropin injection gel): 80–120 units daily for one to three weeks
Oral prednisone: 500–1,250 mg daily divided for three to seven days
"Smoothie Medrol:" 1 g methylprednisolone mixed in smoothie or juice taken orally with breakfast for three to seven days
Dexamethasone: 160–200 mg orally/IV daily divided for three to seven days
| A) | a malignant course. | ||
| B) | few current signs of disease. | ||
| C) | progressive (primary or secondary) course. | ||
| D) | severe relapses who have failed to respond to IV corticosteroids. |
It is now known that B-cell immunity also plays a key role in the pathogenesis of MS. Plasma exchange may be beneficial for relapsing forms of MS in which severe neurologic exacerbations prove refractory to parenteral corticosteroid therapy. It may also be beneficial for some patients with severe, rapidly progressive MS and similar disorders; however, it does not show any efficacy for SPMS or PPMS.
| A) | leukemia and cardiotoxicity. | ||
| B) | liver and thyroid dysfunction. | ||
| C) | injection site reactions and lipoatrophy. | ||
| D) | infusion-related hypersensitivity and anaphylaxis. |
Mitoxantrone, a cytostatic drug and a powerful anti-inflammatory, is used in the treatment of both RRMS and progressive forms of MS [119,120]. It is considered one of the most effective drugs in resolving relapses; however, due to the risks for leukemia and cardiotoxicity, it should only be prescribed to patients with rapidly advancing disease who are refractory to other therapies [121]. Some patients, especially with a subtype of RRMS called rapidly worsening MS, do not respond to immunomodulators and are managed with immunosuppressants, particularly mitoxantrone [122,123].
| A) | baclofen. | ||
| B) | tizanidine. | ||
| C) | dantrolene. | ||
| D) | gabapentin. |
Baclofen and tizanidine are commonly used to treat and reduce spasticity, and the benzodiazepines (e.g., diazepam) also have a beneficial effect. Other possible agents include gabapentin and dantrolene [102]. In general, baclofen is considered the drug of choice for spasticity in patients with MS [152]. An intrathecal baclofen pump may be indicated for patients with unilateral or bilateral phasic lower limb spasticity. Dantrolene should be used with caution because of the potential for hepatotoxicity [102].
| A) | Avoiding alcoholic beverages | ||
| B) | Avoiding spicy and acidic foods | ||
| C) | Increasing caffeine consumption | ||
| D) | Decreasing fluid intake two to three hours prior to bedtime |
Patients who experience nocturia or nocturnal enuresis should be advised to empty their bladder before going to bed and decrease or avoid fluid intake two to three hours prior bedtime. Caffeinated products, alcoholic beverages, and spicy and acidic foods can cause bladder irritation and urinary frequency and should be avoided. If these behavioral strategies are ineffective, treatment with oral desmopressin is indicated [157].
| A) | continue their treatment without pause. | ||
| B) | stop treatment for no more than one month prior to conception. | ||
| C) | be warned that pregnancy can dramatically worsen MS symptoms. | ||
| D) | stop treatment for at least three months prior to conception, if safe. |
If safe, women intending to conceive should stop their MS treatment for at least three months prior to conception. A study conducted in Sweden concluded that pregnancies that were not exposed to the ß-interferon in utero for at least a two-week period prior to conception resulted in healthier infants than pregnancies with such exposure [263]. A small Canadian study found that pregnancies exposed to ß-interferon resulted in a higher number of miscarriages, low birth weight, and prematurity [264]. However, a larger study did not find a significantly higher rate of complications in pregnancies accidentally exposed to immunomodulators [265]. In general, even the higher incidence of complications observed in some studies was only slightly greater than that of the general population. If continued treatment is necessary, modifications to the prescribed regimen (with preference for lower risk options) may be necessary. Many drugs used to treat MS and its related symptoms are contraindicated during pregnancy.