Multiple Sclerosis

Definition of Disease

A chronic inflammatory disease involving degeneration of central nervous system (CNS) myelin, scarring/formation of plaques, and loss of axons is present _{(Mccance et al., 2014)}. 0.1% of the population affected, 2.1 million worldwide, higher in whites, and the etiology is unknown _{(Mccance et al., 2014)}. MS is the most prevalent CNS demyelinating disorder _{(Mccance et al., 2014)}.

Pathphysiology

MS is described as occurring when a previous infectious insult to the nervous system has occurred in a genetically susceptible individual with an abnormal CNS immune _{(Mccance et al., 2014)}. Auto-reactive T and B cells recognize myelin autoantigens and trigger inflammation in the CNS, leading to irreversible tissue damage: ogliodendrocyte injury, demyelination, and axonal degeneration _{(Mccance et al., 2014)}. MS degeneration process begins early and continues to progress throughout life.

Immunopathology

Derived from the experimental autoimmune encephalomyelitis animal model (EAE) _{(Constantinescu et al., 2011)}. Following environmental triggers and genetic susceptibility, activation of myelin specific auto-reactive CD 4+ and CD8+ T cells cross blood-brain barrier and enter the CNS and attack myelin _{(Mccance et al., 2014).} Process is driven by the expression of cell surface integrins (VLA-4) on inflammatory cells that mediate their binding to the vascular cell adhesion molecule (VCAM-1) expressed on endothelial cells_{(Gold et al., 2011).} VCAM-1 expression is induced by TNF-α and in IFN-γ during inflammation. Matrix metalloproteases (MMPS) are released by the Tcells to facilitate passage through the extracellular matrix_{(Gold et al., 2011).}

After entry into the CNS, T cells are reactivated on encountering CNS-related auto-antigentic peptides within class 2 molecules of the MHC expressed by antigen/dendritic cells_{(Gold et al., 2011)}. Production of IL-17 by Th17 cells play an important role within this process _{(Mccance et al., 2011)}. Myelin disruption occurs, leading to additional inflammation and activation of complement and specific B lymphocytes to site of tissue injury_{(Gold et al., 2011)}. As the inflammatory changes in the CNS increase, loss of brain volume progresses. Demyelination disrupts Na+, Ca++, and K+ ion channels: calcium influx is proinflammatory and neurotoxic_{(Mccance et al., 2014)}. The immune cells also produce glutamate, a neurotoxin _{(Mccance et al., 2014)}.

Genetics

Not inherited in a Mendelian fashion, first degree relatives have a 1-5 times increased risk of MS, while the concordance rate in monozygotic twins is 35% _{(Gold & Wolinsky, 2011)}.

HLA

A genetic link exist in the human leukocyte antigen (HLA) complex: a large cluster of genes responsible for many immune functions (Mccance et al., 2014). Patients carrying the class 2 major histocompitability complex (MHC) HLA-DR2 genes are susceptible to MS _{(Gold et al., 2011)}. Several risk loci beyond the MHC have been identified, including the interleukin-7 (IL-7) receptor, interleukin-2 receptor alpha chain (IL2RA) and CD58 _{(Gold et al., 2011)}.

Epidemiology

The cause of MS is unknown, however, along with several genetic polymorphisms involved, Vitamin D deficiency, cigarette smoking, and viral infections are know to be associated with MS.

Viral infections Strong correlation that suggests influenza A and Epstein Barr Virus (EBV) viral infections are associated with a high occurrence of exacerbation in MS patients _{(Oikonen et al., 2011)}. Also, studies have correlated an association of varicella zoster virus with MS _{(Kang et al., 2011)}

Geographic Factors MS is relatively common in Europe, U.S., Canada, New Zealand _{(Wingerchuk, 2011)}. However, rare in tropical regions: this geographical distribution of MS supports an association between latitude and regional disease prevalence _{(Wingerchuk, 2011)}.

Sunlight/Vit. D Correlates or contributes to the latitude gradient of MS prevalence _{(Wingerchuck, 2011)}. Most people with established MS have relatively low Vitamin D levels and the level appears to decline over time _{(Wingerchuk, 2011)}.

Disease described/classifications

Along with the signs & symptoms listed below, the major classifications/descriptions of MS are based on the disease pattern: relapsing-remitting, primary progressive, secondary progressive and progressive relapsing _{(Mccance et al., 2014)}.

Sign and Symptoms

MS occurs between 20 and 40 years of age (peak at 30 years). Male to female 1:2 _{(Mccance et al., 2014)}. The signs and symptoms of MS can be categorized into established syndromes within location of damage.

Optico-Spinal (OSMS) presents with optic nerve and spinal cord axonal loss, evolves rapidly over hours to days. Symptoms include impaired central vision, optic papillitis, and optic neuritis _{(Mccance et al., 2014)}. Brainstem lesion common symptoms (III through XII) include Internuclear opthalmoplegia, nystagmus, diplopia, eye pain, and dysarthria _{(Mccance et al., 2014)}. Other brainstem lesion residuals include vomiting, tinnitus, facial weakness/sensory deficit _{(Mccance et al., 2014)}.

Spinal MS is the second most common type, involving spinal tracts and dorsal column _{(Mccance et al., 2014)}. Weakness,numbness, and stiffness in limbs along with lower limbs more affected than upper limbs. Lhermitte phenomenon described as an electric shock down the back and to the legs_{(Richman & Schub, 2013)}. Spastic paraparesis is the most common neurological finding in MS _{(Mccance et al., 2014)}. Others include\ spastic bladder, urgency, hesitancy preceding incontinence, constipation and impotence_{(Mccance et al., 2014)}.

Motor deficits/Cerebellar include deep tendon hyperreflexia, diminished cremasteric reflex, clonus, poor coordination, presence of Babinski reflex and Hoffman's sign, spasticity, ataxia, impaired speech/dysphagia _{(Richman & Schub, 2013)}. Other cerebellar MS symptoms include the Charcot triad: dysarthria, intention tremor, and nystagmus_{(Mccance et al., 2014).}

Cognitive deficits include dementia and depression _{(Richman & Schub, 2013)}.

Diagnosis

Known as the McDonald criteria _{(Mccance et al., 2014).}

Assessment onset of symptoms, duration, including pain and fatigue_{(Richman & Schub, 2013)}. Signs and symptoms indicating disease with 2 or more episodes lasting at least 24 hours and occurring at least 1 month apart _{(Richman & Schub, 2013)}.

Lab Analysis of CSF aspirated during lumbar puncture will indicate elevated immunoglobulins, myelin debris, and mildly elevated or normal protein _{(Richman & Schub, 2013)}. Immunoglubulin G index is found in 2/3 of individuals with MS and oligoclonal bands of IgG on electrophoresis in more than 90%_{(Mccance et al., 2014)}.

Diagnostic Studies MRI and CT scan may indicate plaques and/or glial scars in the brain and spinal cord. VEP test may diagnose optic nerve demyelination _{(Richman & Schub, 2013) (Mccance et al., 2014)}.

Treatment

Overall, provide symptomatic relief and reduce risk of complications: permanent neurological damage _{(Richman & Schub, 2013)}. Acute relapses treated with corticosteroids: methylprednisolone. Oral and injectable disease modifying drugs are used to decrease relapse, promote remyelination, suppress B&T cell function, prevent demyelination. Options for immunosuppression include interferons (Avonex, Rebif, Betaseron), glatiramer, natalizumab, and and fingolimod _{(Richman & Schub, 2013)}.Vitamin D for reduction of risk _{(Mccance et al., 2014)}.

Pain and fatigue Can be assisted or relieved with analgesics, ice, heat, TENS. Amanadine, modafinil as ordered to combat fatigue _{(Richman & Schub, 2013)}.

Bladder dysfunction & constipation can be relieved by avoiding bladder irritants, timed voiding, regulating fluid intake, anti-cholinergic medications (Ditropan), and constipation assisted with stool softeners/fiber _{(Richman & Schub, 2013)}.

Spasticity can be relieved with baclofen or anti-epileptics _{(Richman & Schub, 2013)}.

Referrals for physical therapy (PT), occupational therapy (OT), and speech therapist based upon disease progression _{(Richman & Schub, 2013)}.

Recommendations & Further Readings

National Multiple Sclerosis Society

References

Constantinescu, C., Farooqi, N., O'Brien, K., & Gran, B. (2011). Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). British Journal Of Pharmacology, 164(4), 1079-1106. doi:10.1111/j.1476-5381.2011.01302.x

Gold, R. R., & Wolinsky, J. S. (2011). Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurologica Scandinavica, 124(2), 75-84. doi:10.1111/j.1600-0404.2010.01444.x

Kang, J., Sheu, J., Kao, S., & Lin, H. (2011). Increased risk of multiple sclerosis following herpes zoster: a nationwide, population-based study. Journal Of Infectious Diseases, 204(2), 188-192. doi:10.1093/infdis/jir239

McCance, K., Huether, S., Brashers, V., & Rote, N. (2014). Pathophysiology: The biologic basis for disease in adults & children (7th ed.). St. Louis, MO: Elsevier Saunders.

Oikonen, M., Laaksonen, M., Aalto, V., Ilonen, J., Salonen, R., Erälinna, J., & ... Salmi, A. (2011). Temporal relationship between environmental influenza A and Epstein-Barr viral infections and high multiple sclerosis relapse occurrence. Multiple Sclerosis (Houndmills, Basingstoke, England), 17(6), 672-680. doi:10.1177/1352458510394397

Richman, S., & Schub, T. (2013). Multiple Sclerosis. CINAHL Plus with Full Text. Retrieved from http://eds.b.ebscohost.com.ezproxy.colostate-pueblo.edu/eds/pdfviewer/pdfviewer?sid=2f5e6cf2-49af-404f-8d2d-bca9ee69674d%40sessionmgr198&vid=3&hid=101

Wingerchuk, D. M. (2011). Environmental factors in multiple sclerosis: epstein-barr virus, vitamin D, and cigarette smoking. Mount Sinai Journal Of Medicine, 78(2), 221-230. doi:10.1002/msj.20240

Created by Ryan Morris, CSU-Pueblo Nursing Graduate Student