Multiple Sclerosis


Chapter 199

Multiple Sclerosis



Barbara S. Bishop



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.13 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).13 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.46 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



Box 199-1


Clinical Courses of MS



Radiographically isolated syndrome (RIS): Presence of magnetic resonance imaging (MRI) lesions specific to MS that may meet the MRI diagnostic criteria for MS without clinical symptoms. Sixty-five percent of patients convert to MS in 5.3 years.


Clinically isolated syndrome (CIS): Acute or subacute focal neurologic event indicative of demyelination and often associated with clinically silent lesions on MRI. Up to 90% of MS patients have CIS on presentation.


Relapsing-remitting MS (RRMS): Course punctuated by clinical relapses (exacerbations) followed by periods of clinical remission; most common type; 85% of MS patients have RRMS at time of diagnosis.


Primary-progressive MS (PPMS): Accumulating disability from initial presentation without clearly defined relapses or remissions. Approximately 10% of MS patients have PPMS.


Secondary-progressive MS (SPMS): Thought to be the natural evolution of RRMS. It represents a progressive course with or without relapses. Natural history states that 50% of RRMS will convert to SPMS, and 90% after 25 years.


Progressive-relapsing MS (PRMS): Steadily progressive from onset, but also with acute attacks. Approximately 5% of MS patients have this type.


Benign: Expanded Disability Severity Scale (EDSS) score ≤3 for more than 10 years. This definition does not take into account domains of fatigue, cognition, mood, pain, social functional levels, and radiographic changes. Studies have supported decline in all aforementioned domains. In addition, approximately 50% of patients with “benign” MS progress to having EDSS scores ≥6.0 or progress to SPMS within 20 years.


Data from Compston A, Coles A : Multiple sclerosis Lancet 372:1502-1517, 2008; Moses H Jr, Picone M, Smith V: Clinician’s primer on multiple sclerosis: an in-depth overview, Denver, CO, 2008, Consensus Medical Communications; Okuda DT, Mowry EM, Beheshtian A, et al: Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology 72(9):800-805, 2009; Leahy H, Garg N: Radiologically isolated syndrome: an overview. Neurol Bull 5:22-26, 2013; and Costella K, Halper J, et al: The use of drug modifying therapy in multiple sclerosis: principles and current evidence. Denver, 2014, Consortium of Multiple Sclerosis Centers (CMSC). www.mscare.org.


imageSpecialist 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.13,9,10



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.13,15


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 management15,16 (see Table 199-1).



TABLE 199-1


Symptomatic and Rehabilitative Therapies for Multiple Sclerosis*





















































Symptom Description Treatment Modalities
Ataxia

Bladder Bladder: hesitancy, urgency, frequency incontinence; reported rates 52%-97%
Bowel Bowel: irregular bowel is common; constipation, loose stools; constipation may aggravate bladder issues; reported rates 35%-68%
Cognitive dysfunction

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
Fatigue

Pain and paresthesias

Sexual dysfunction

Spasticity

Tremor

Weakness Focal limb weakness caused by underlying demyelination and axonal loss

Oct 12, 2016 | Posted by in CRITICAL CARE | Comments Off on Multiple Sclerosis

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