Definition and Epidemiology

Multiple sclerosis (MS) is a chronic progressive inflammatory and neurodegenerative disease affecting the central nervous system (CNS). The hallmark lesion in MS, called a plaque, was first described in the 1800s.¹ Multiple lesions are seen in multiple locations, hence the name multiple sclerosis. On histologic examination, the lesions are characterized by inflammation, demyelination, axonal injury and transaction, axonal loss, and gliosis.^1–3 MS is thought to be a complicated interaction among the autoimmune system, genetic variables, and environmental factors.¹ Clues to the cause of MS come from the worldwide and nonrandom pattern of this disease, studies of structural and functional changes within the CNS, immunologic studies, and genetic studies (particularly studies of families and twins).^1–3 To date, no single causative factor has been identified. It has been postulated that low vitamin D levels, exposure to Epstein-Barr virus (EBV) in preadolescence, and smoking are significant contributing environmental factors in MS. More than 100 genes have been identified that are associated with MS.^4–6 Box 199-1 describes the types of presentation and clinical courses of MS. The onset of MS is likely to occur between 20 and 50 years of age. MS affects three times as many women as men. It can also occur in the pediatric and geriatric populations. MS affects up to 450,000⁸ Americans and approximately 2.5 million persons worldwide. The worldwide pattern of MS shows that it is less common near the equator, and the highest incidence is across northern Europe, North America, and Australia. It occurs most commonly in Caucasians.^1,2 African Americans tend to have more aggressive disease courses.⁷

Specialist referral is indicated for all suspected cases of MS.

Pathophysiology

MS has historically been thought of as an inflammatory disease of the white matter of the CNS. This paradigm has changed. It is not only inflammatory but also neurodegenerative and involves not only the white matter but the gray matter as well.

The sequence of events has become better clarified but is still not thoroughly understood. Presently, it is believed that a triggering event, most probably from the environment, activates the inflammatory process outside the CNS. This inflammatory process includes T- and B-cell activity, macrophages, natural killer cells, and others, demonstrating a complex and encompassing immune response from both the innate and adaptive immune systems. There is degradation of the blood-brain barrier, allowing the proinflammatory cytokines to penetrate the CNS. Once the proinflammatory cytokines are in the CNS, reactivation of the inflammatory process occurs, leading to demyelination and axonal destruction. Both the inflammatory and degenerative processes are seen early and simultaneously and often are felt to be interrelated. There is some support that they may also be independent of each other.⁸ Regardless of the process, as the disease progresses, inflammation downregulates and neurodegeneration escalates. The process by which this occurs is not fully understood at this time.^2,3,9

Recovery in early disease occurs because of the capacity of the CNS to functionally reorganize, compensate for axonal loss, and remyelinate. Remyelination is often incomplete and variable, and over time, axonal degradation becomes significant. Compensation is no longer possible. Permanent disability develops. It is believed that axonal degradation is responsible for permanent disability.^1–3,9,10

Clinical Presentation

There are four clinical courses of MS (see Box 199-1): relapsing-remitting (RRMS), primary-progressive (PPMS), secondary-progressive (SPMS), and progressive-relapsing (PRMS). RRMS is the most common form of MS. Natural history of the disease shows that 50% of MS patients will progress to SPMS within 11 to 15 years.^1,8

At presentation, patients often have what is now referred to as a clinically isolated syndrome (CIS) or first clinical episode. Patients typically have a focal neurologic deficit such as the eye pain or visual disturbances seen with optic neuritis. Sometimes the initial presentation is multifocal.^1,11 Magnetic resonance imaging (MRI) demonstrates multiple lesions consistent with MS. This is important, because it is now possible to treat patients at this very early stage of the disease process.^6,12 Radiographically isolated syndrome (RIS) is now reaching the literature. It is defined as the presence of MRI lesions specific to MS and may meet the MRI diagnostic criteria for MS; however, no clinical symptoms consistent with MS can be identified in the patient’s history. Often these patients are undergoing MRI for some unrelated issue such as trauma or migraines. Currently, patients with RIS are not routinely being treated with disease-modifying therapy (DMT). Data to date suggest that 65% of patients will convert to MS within 5.3 years and 88% will convert in 14.1 years. Median time to conversion to CIS is 5.4 years.^13,14

The most common presenting symptoms include visual disturbances and eye pain that comes and goes, pain in the neck or back, paresthesias or weakness of the limbs, or facial pain along the course of the trigeminal nerve. Other symptoms commonly seen include sensory symptoms (paresthesias), diplopia (intranuclear ophthalmoplegia), nystagmus, unsteady gait, or bowel or bladder dysfunction. Associated findings that increase the likelihood of MS include unexplained excessive fatigue, temperature or heat sensitivity, history of bandlike sensations around the waist (commonly referred to as the “MS hug”), dysarthria, muscle spasms, cognitive disturbances, and sexual dysfunction.^1–3,15

The initial presentation of MS can often go unrecognized or is attributed to other causes, especially if the presenting symptom is vague, such as sensory distortion, bowel or bladder dysfunction, or cognitive impairment. Initial symptoms are sometimes so vague, transient, or mild that the patient may not seek medical advice.

Symptoms of MS are unpredictable and variable. As the disease progresses, a variety of signs and symptoms will require ongoing management^15,16 (see Table 199-1).

TABLE 199-1

Symptomatic and Rehabilitative Therapies for Multiple Sclerosis*

Symptom	Description	Treatment Modalities
Ataxia	Incoordination and disturbance of balance and gait Worsened by spasticity, weakness, and fatigue Falls common	Home evaluation necessary to assess safety and fall risk Rehabilitation services for gait and balance; may work with balance balls and other techniques Medications ineffective Avoid alcohol
Bladder	Bladder: hesitancy, urgency, frequency incontinence; reported rates 52%-97%	Bladder: avoid dietary irritants such as caffeine and spicy foods; use toileting schedule; refer to urologist for formal workup; screen for UTI; fluid restriction at bedtime; biofeedback and Kegel exercises; clean intermittent catheterization; botulinum toxin; nerve stimulation devices Drug therapy: anticholinergics, antimuscarinics, and alpha blockers
Bowel	Bowel: irregular bowel is common; constipation, loose stools; constipation may aggravate bladder issues; reported rates 35%-68%	Bowel: fiber, stool softeners, laxatives, glycerin suppositories; bowel training programs, diet counseling, exercise Drug therapy: anticholinergic or muscle relaxant properties, such as oxybutynin, tolterodine, propantheline, antidiuretic hormone; botulinum toxin injections
Cognitive dysfunction	40%-70% of MS patients have some degree of cognitive impairment; executive functioning and memory are most common Can be a source of disability	Neuropsychological evaluation is important to define problem areas and provide recommendations; compensatory and restorative methods can be helpful; brain exercises such as those on Lumocity.com and CogMed.com Treat underlying disorders that can contribute to problem, such as depression, anxiety, fatigue, sleep disorders Adherence to DMT; some have been shown to slow cognitive decline Drug therapy: acetylcholinesterase inhibitors have not been found effective in larger studies
Depression	Endogenous as a result of changes in brain chemistry; may also be exogenous; higher incidence (56%) and rates of suicide than in other chronic or neurologic diseases	Antidepressants Counseling
Fatigue	Rates reported to be 65%-97% Highly debilitating; often the reason for disability Cause unknown Aggravated by depression, anemia, hypothyroidism, sleep disorder, elevated core body temperature	OT for energy conservation techniques Cooling vest or cap Staying well hydrated and drinking ice-cold water to bring down core body temperature Avoidance of heat Treat underlying problems Consider changing DMT if severe; glatiramer acetate may have less effect on fatigue than interferons Drug therapy: amantadine, methylphenidate, modafinil, armodafinil , fluoxetine (even if depression is not present)
Pain and paresthesias	Reported rates as high as 85% Trigeminal neuralgia and other forms of neuropathic pain (burning, numbness, tingling), migraines, spasms, musculoskeletal pain	Pain from spasms relieved with antispasmodics (discussed previously) PT and assistive devices Yoga, Pilates, tai chi for musculoskeletal pain Drug therapy: neuropathic pain—carbamazepine, gabapentin, pregabalin, topiramate, lamotrigine, lidocaine patch, duloxetine, tricyclic antidepressants; musculoskeletal pain—gabapentin, lidocaine patch, duloxetine, NSAIDs, muscle relaxants
Sexual dysfunction	Up to 90% in men and 85% in women Lack of interest or arousal Changes in self-esteem Problems with intimacy Impotence, anorgasmia, vaginal dryness Decreased or altered sensations Functional difficulties: spasms, bladder control	Try to coordinate symptomatic treatments to sexual activity (antispasmodics, self-catheterization); increased stimulation using vibration can be helpful; counseling may be necessary Drug therapy: erectile dysfunction medications for men, such as tadalafil, vardenafil, sildenafil citrate; remove offending medications if possible, such as SSRIs
Spasticity	Reported rates: 40%-85% Stiff, slow movements; spasms	PT and assistive devices Yoga, Pilates, tai chi Drug therapy: baclofen intrathecal pump implantation; botulinum toxin injection; baclofen (Lioresal), tizanidine, dantrolene (Dantrium), benzodiazepine, gabapentin, levetiracetam
Tremor	May involve UE, LE, trunk, head, and voice and may be incapacitating Very difficult symptom to manage	OT help with weighted equipment and environmental modification strategies Deep brain stimulation can be considered and can be very effective for controlling tremor but is not FDA approved for MS tremor at this time. Drug therapy: most drugs are ineffective for MS tremor; some drugs that have been tried with limited success include propranolol and other beta blockers, clonazepam, primidone, ondansetron, isoniazid, and glutethimide
Weakness	Focal limb weakness caused by underlying demyelination and axonal loss	Rehabilitation services for strength training and adaptive devices such as braces and ambulatory assistive devices Keep core body temperature down; heat disrupts conduction For footdrop, ankle-foot orthoses can be helpful; WalkAide and Bioness systems, functional electrical stimulation devices, have been beneficial Drug therapy: dalfampridine, a potassium channel blocker, has recently been approved by the FDA to improve walking in MS; it is the only drug in its class Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related Related posts: Hypotension Corns and Calluses Seborrheic Dermatitis Dry Skin Surgical Office Procedures Psoriasis Tags: Primary Care A Collaborative Practice Oct 12, 2016 | Posted by admin in CRITICAL CARE | Comments Off on Multiple Sclerosis Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access