Author(s): Zahra Pah Lavan

Abstract:

Zahra Pah Lavan gives an overview of Multiple Sclerosis and the treatments available. Zahra Pah-Lavan RN, BSc (Hons) is a freelance writer. Article accepted for publication: September 2005

Keywords:

Progressive disease Spasticity Myelin sheaths

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system (CNS), with symptoms that can range from relatively benign to devastating (Compston & Coles, 2002). Current estimates are that approximately 2.5 million people worldwide have MS, with up to 62,000 cases in the UK (Compston & Coles, 2002; Toosy & Thompson, 2000).

Persons with MS may see a wide range of medical professionals depending on their symptoms (Table 1), the way MS progresses and the extent of their physical disability. A specialist or generalist nurse's role in hospital, community or long-term care is critical in providing individuals with MS and their carers with ongoing and supportive education on the disease. Nurses can work within the multidisciplinary team without losing sight of the holistic approach necessary for each individual's unique MS management (UK Multiple Sclerosis Specialist Nurse Association et al., 2001).

The name 'multiple sclerosis' signifies both a number (ie more than one) and a condition (of the scarred myelinated areas in the CNS with sclerosis being the Greek word for scarring or hardening) (www.NINDS.nih.gov). When myelin is damaged, nerve communication is disrupted and neurological transmission of messages may be slowed or blocked completely, leading to diminished or total loss of bodily functions that are controlled by areas of the CNS (Waugh & Grant, 2001).

MS affects one in 1,000 people in Western countries (USA, Europe & Australia) and is generally more common in caucasians and women (McDonald, 1998). It does not occur as frequently in every country throughout the world and seems to be related to how far a country is from the equator becoming more common the farther away a country is (Waugh & Grant, 2001; Sadovnick & Ebers, 1993). MS usually starts between the ages of 20 and 40 years but can make its first appearance in early childhood or after age 60 (McDonald, 1998). Some studies suggest that there may be a connection between where a person lived for the first 15 years of his/her life and the incidence of MS (Alvarez-Lafuente et al., 2004; Gaudet et al.,1995; Waugh & Grant, 2001).

Causes of MS
Despite a great deal of research, a specific cause of MS has not yet been determined (Alvarez-Lafuente et al., 2004). Environmental studies suggest that there is a triggering factor in the environment, such as toxins causing MS to manifest in those whose immune systems are genetically predisposed to it (Compston, 1997). It is hypothesised that, at the time of or immediately following puberty, patients acquire an infection with a long latency period. Or, conversely, people in some areas may come in contact with an unknown protective agent during the time before puberty (Waugh & Grant, 2001). Other studies suggest that the unknown element may actually be genetic predilection reflecting racial and ethnic susceptibility factors (Gold, Rieckman & Rieckman, 2000; Swanborg, Whittum-Hudson, Hudson. 2003).

Anatomy and physiology
Neuron cells: The brain, spinal cord nerves are made up of neuron cells which transmit information and control bodily functions. Each neuron has several branching structures called dendrites (responsible for receiving information from other neurons and the body), and a long arm-like nerve fibers called an axon (along which electrical signals travel passing information and instructions from the CNS to the body). Axons have a protective coating of myelin, wrapped around them like insulation to help them with their work (Waugh & Grant, 2001).

Central nervous system (CNS): This is made up of the brain and the spinal cord through which we can pick up signals from the outside world such as what we can see, smell, taste, hear and feel. The CNS also coordinates all our conscious and unconscious activities such as moving, talking, thinking, remembering and the reflex actions that happen without us thinking about them. Any

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damage to the CNS whether it is to the nerve cell or to the myelin sheath, will stop the transfer of messages carried by the nerves and produce a constellation of neurological symptoms. It is believed that in MS the nerves in the CNS are stripped of their myelin coating due to autoimmune disease (Thibodeau & Patton, 2002; Waugh & Grant, 2001).

The immune system: A complex network of specialised cells and organs - defends the body against attacks by antigens such as bacteria, viruses, fungi, and parasites. Once the immune system recognises an antigen, the first defence is an inflammatory reaction followed by the production of antibodies and migration of special cells, such as T-cells, to fight off the threat. In autoimmune disease the system fails and it begins to consider parts of itself as foreign and launches an attack on them (Thibodeau & Patton, 2002; Waugh & Grant, 2001).

Blood-Brain barrier: Although the brain is continually supplied with nutrients through the circulating blood, no blood cells cross through the walls of the blood vessels into the brain. In MS, a breach in the barrier between blood and brain brings, for the first time, the white blood cells of the immune system into direct contact with the myelin coats of nerve cells. Not having encountered myelin before, the white blood cells regard it as foreign and launch an attack stripping the nerve fibres of their protective myelin sheath. Demyelinated fibres are unable to carry out their function of carrying messages from the CNS to the rest of the body, and the symptoms of MS result (Waugh & Grant, 2001; Toosy & Thompson, 2000).

Cycle of damage and recovery: Myelin is produced by highly specialised cells (oligodendrocytes) and unfortunately, an adult brain has a limited supply of these cells which themselves only have a limited life when they are actively producing myelin. Once the inflammation within the CNS subsides, cells within the CNS can begin to repair the damaged myelin (remyelination). As the disease advances, the production of myelin cannot keep pace with its destruction resulting in an incomplete recovery of the affected function or permanent damage to the axons and complete loss of electrical signals. It is believed that permanent disability in MS could be the result of both ongoing demyelination and axonal injury (Table 2, Thibodeau & Patton, 2002; Waugh & Grant, 2001).

How is MS diagnosed?
MS diagnosis is highly dependent on the accuracy of the patient's medical history and the physician's skill in eliciting and evaluating it, however diagnosis is often delayed due to the transitory nature of the disease and the lack of specific

Table 2: Different forms of MS

1. Relapsing-remitting MS (RR-MS) Shows clearly defined relapses with some amount of recovery. It is the most common form of MS diagnosed. 2. Secondary progressive MS Initially follows a RR-MS course but over time a variable but continued loss of physical & cognitive functions starts to take over & relapses become less common. 3. Primary progressive MS Shows no relapse, & over the years there is continual loss of physical & cognitive functions. Source: Confavreux et al, 2000

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diagnostic test – specific symptoms. During a neurological consultation, Magnetic Resonance Imaging (MRI) scans, lumber puncture or evoked potentials tests may be requested (Basics of best practice in the management of Multiple Sclerosis, 1999).

MRI uses a strong magnetic field to create images of the brain and spinal cord showing defects in the white matter including patches of inflamed myelin. However, the link between the amount of disease activity shown on the MRI scan and the progress of the disease is not very clear and at present it is not possible to use the results of MRI to predict how the disease will develop (Frohman et al., 2003; Brex et al., 2002). As lesions can also occur in several other neurological disorders such as diabetes, Lyme disease, pernicious anaemia and spinocerebellar ataxias to name but a few (Waugh & Grant, 2001), they are not absolute evidence of MS. The MS diagnostic criteria (Association of British Neurologists, 2001) therefore sets out that neurological evidence of lesions or plaques in at least two distinct areas of the CNS white matter, evidence that the plaques have occurred at different points in time, and most importantly, that these plaques have no other reasonable explanation thus ruling out other illnesses that mimic MS.

Lumbar puncture involves taking a sample of the cerebrospinal fluid to check for cellular and chemical abnormalities including increased white blood cells and higher-than-average amounts of protein, especially myelin basic protein and an antibody called immunoglobulin G (Waugh & Grant, 2001; Basics of best practice in the management of Multiple Sclerosis, 1999). Evoked potentials measure responses of axons to the passage of nerve impulses from the brain to a specific part of the body that controls a particular body function, such as hearing, sight or movement. This means that when MS is present it is possible to see whether certain nervous impulses are slowed down in the demyelination of axons (Basics of best practice in the management of Multiple Sclerosis, 1999).

Finally, symptoms like numbness, tingling, or fatigue, will not be seen on any diagnostic tests and there may be cases where a person with the clinical symptoms of MS does not meet all the criteria to confirm a diagnosis of MS. A clinical diagnosis of MS may take years with a physician observing a person over a period of time before reaching a diagnosis of MS (Noseworthy et al., 2000).

MS progression
The course of the disease, and the development of disability, varies depending on the severity or location of inflammation or how quickly the myelin breaks down. After an initial event, each following episode of symptoms is called a relapse. When the inflammation is resolved, the symptoms may subside (remission). Remission may not mean a return to the way things were before the relapse and residual symptoms may be left behind (Waugh & Grant, 2001; Noseworthy et al., 2000).

It is possible to make a rough overall distinction between different types of MS according to the progress of the disease (Table 2). However, because MS varies so much between individuals, it is nearly impossible to predict how MS might affect a person or progress in the future (Confavreux et al., 2000).

Symptoms are one way to mark the progression of disease in MS. However, MS can also progress silently through axonal loss. The brain can adapt to and

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Table 1: Possible symptoms of MS
Vision disturbances and optic neuritis • One of the earliest symptoms of MS which may start with blurred vision followed by vision loss due to an inflammation of the optic nerve. • Rarely involves both eyes simultaneously. • After the initial symptoms, there is a gradual improvement, but recovery is not always complete. • Stress, fatigue or fever, may cause the blurred vision to return. This does not necessarily mean that the MS is active again. Rather, it may be the result of permanent disability that has accumulated over time. Loss of muscle strength in arms and legs • MS often affects the axons that control muscle movement. • Weakness may progress to partial or complete paralysis. Tremors, shaking or trembling of a limb or the head • May come and go and impair mobility. • Ataxia is associated with difficulty in balance and co-ordination. Spasticity Can occur either as sustained stiffness caused by increased muscle tone or as spasms that come and go, especially at night. • Occurs when opposing groups of muscles contract and relax at the same time. • Increased stiffness in the muscles means that a great deal of energy is required to perform daily activities. Impairment of the sense of touch • One of the earliest symptoms of MS. • The sensory axons in CNS provide the sense of touch in all skin, and the ability to feel cold or heat on all parts of the body. • When axons are damaged the sense of touch may be replaced by feelings of burning and crawling sensations, tingling, feelings of swelling or numbness. • Parts of the body may feel burning or cold, even though there is no heat or chill present. • If severe neurological damage to the myelin sheath takes place, then numbness may remain. Sexual Difficulties (male and female) • Includes impaired sensation, diminished orgasmic response, and decreased sexual drive loss of sexual interest. Pain • Burning pain in the arms and legs (due to damage to the sensory tracts in the spinal cord). • Trigeminal neuralgia (due to damage to the nerves of the face).	• Spasticity causes extra tension in arm and leg muscles which can be painful. • If MS has impaired the ability to walk, the extra strain in the muscles of a person’s back and legs can become painful. • Pain in the neck and shoulder muscles extending down the back, in the joints and muscles (Fibromyalgia). Bladder dysfunction • Includes increased frequency of urination, urgency, dribbling, hesitancy, inability to completely empty the bladder and incontinence. Bowel dysfunction • Includes constipation, diarrhoea and incontinence. Depression and psychotic disorders (manic-depression and paranoia) • Depression can intensify many symptoms. • May be linked directly to physical changes in the brain caused by MS. • MS-related lethargy and fatigue may be mistaken for depression or heighten its effects. • Depression may be linked to some treatments for MS that are prescribed to help to slow the progression of symptoms and/or disability. • Understandably, there may also be an emotional reaction to having the illness and coping with the symptoms and the challenges they represent. Emotional Liability and inappropriate euphoria and despair • Due to demyelination in the brainstem, that controls facial expression and emotions. • Usually seen in severe cases. Cognitive Dysfunction • Involves reasoning, verbal fluency and slower speed of thinking difficulties with concentration, attention, memory, and poor judgment. Fatigue • May be both physical and psychological and not often immediately identified as being caused by MS. • May take the form of a constant and persistent tiredness. • A person’s energy is used up every day with just a little exertion. Overdoing activities • In healthy people the body shuts down when the anaerobic threshold is reached as a lot of pain is experienced. • This warning does not occur activity is continued as no pain is experienced and the lactic acid builds up, and the body ends up recirculating carbon dioxide.
References: Soderstrom et al., 1998; Rukwied et al., 2003; Rae-Grant et al., 1999; Amato & Zipoli, 2002; Gold, Rieckmann, & Rieckmann, 2000; Johnson et al., 1996; Mahler & Benson 1990; Schurmann, Basar Eroglu & Basar, 1997; Coffey et al., 1987.

compensate for some level of damage, with symptoms being highly dependent on where the damage takes place since different parts of the brain are responsible for different activities. So a person with MS can look and feel fine, yet his or her disease may be active (Noseworthy et al., 2000).

Not all symptoms listed in Table 1 affect every MS patients and complaints may appear in various combinations depending on the area of the nervous system affected. Symptoms may be mild or severe, of long duration or short, persistent and progressive or stop from time to time (relapse & remission) and may even remit completely, leaving no residual damage, or partially leaving degrees of permanent impairment (Waugh & Grant, 2001; Compston & Coles, 2002). The erratic symptoms of MS can affect the entire family and be an emotional drain on both patient and carer (www.msfacts.org).

Can MS be treated?
Despite great strides in our understanding of MS, it still remains a lifelong disease for which there is no cure. Many patients do well with no therapy at all, especially since many medications have serious side effects (Hartung et al., 2002; Ghalie et al., 2002). Furthermore, naturally occurring or spontaneous remissions make it difficult to determine therapeutic effects of treatments, which manage symptoms and/or modify the progression of the disease. The National Institute of Clinical Excellence (NICE, 2002 & 2003) has ruled that disease modifying therapies (DMT's) such as interferon beta and glatiramer acetate should not be available on the NHS in England and Wales as they are not cost-effective. As a result the risk-sharing scheme was born, where people with MS who meet the criteria set out in guidelines from the Association of British Neurologists can be enrolled on the scheme and receive either interferon beta or glatiramer acetate treatment.

MS being a disease with a natural tendency to remit spontaneously, with no universally effective treatment and no known cause - opens the door to an array of treatments and cures from special diets, fish oils to magnetic field therapy, neural therapy and oxygen therapy. There is currently no supporting evidence for effectiveness of such therapies (MS Society, 2003). Life events have been implicated in the onset of MS including:

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Stress: During periods of stress, fatigue or fever, certain symptoms may return or be exacerbated, however, there is no evidence that daily stress or trauma causes MS or affects its course (Hartung et al., 2002).

Pregnancy: MS generally strikes during childbearing years, but there is no evidence that pregnancy and childbirth affect the overall course of the disease nor does MS hinder a woman's chance of becoming pregnant and carrying a child to full term. However, MS medications would need to be stopped as they can cause birth defects and can be passed to an infant via breast milk. Another consideration would be bringing-up a child with the additional challenges that MS can impose including the times when the MS causes people to feel less well or more tired, or if the MS becomes more progressive in the future (www.MSActiveSource.com).

Research
Currently genetic risk factors and their possible modification, environmental triggers, mechanisms of repair of the damaged blood-brain barrier and remyelination of the axons, re-educating the immune system so that it does not attack myelin, are being investigated. Furthermore, many treatments are in the experimental stages or are undergoing clinical trials.

Diagnosis of an incurable disease with potential for disability associated with loss of bodily control can cause many understandable reactions for people with MS and their carers, which at times involves young children or single parent families. But just as the symptoms and course of MS can be unpredictable, so people and carers' reactions may vary. MS is a journey into the unknown as it is impossible to predict the nature, severity or timing of progression in a given patient. With appropriate multidisciplinary management, nurses can play a key role in supporting individuals and their carers to adjust to new routines or environments in the face of disruptive symptoms (Toombs, 2004) and to grieve for the past but also to look forward and establish new roles (Jarrett, 2003).

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