Pathophysiology for Occupational Therapists: Multicple Sclerosis

Definition of condition

     Multiple Sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system(CNS) (Torres & Salazar, Bittner, Zozulya, Weidenfeller, Wiendl, Fahkle, 2008)

MS is an insidious disease where large, multifocal, demyelinated plagues, oligodendrocyte loss and axonal degeneration occur on the nerve fibres of the CNS. MS occur when the integrity of the blood- rain barriers is compromised permitting the invasion of monocytes and T cells to the brain parenchyma, resulting in health deficits in an individual.

Lesion sights may occur at the cerebrum, optic nerve, cerebellum, brain stem and spinal cord.

https://ot-lwwhealthlibrary-com.ezproxy1.acu.edu.au/content.aspx?sectionid=136769195&bookid=1898

The demyelination means degrading of the myelin sheath (an insulating fatty matter that surrounds the neuron). This stops or slows down nerve conduction thus obstructing and preventing messages passed around the body.

There are four types of MS.

1. Relapsing- Remitting MS

 This refers the unpredictable exacerbations attacks during which new symptoms appear or existing symptoms become more severe. Relapsing- remitting MS can vary in time (days or months) however partial or total remission can occur.

2. Secondary Progressive

This is the most common form of MS, present in 60% of patient diagnoses. It involves the progressive acquisition of disability later in the course of the disease may occur. This often associated with superimposed relapses, where the symptoms be unpredictable of time or severity. 

3. Primary progressive

 This refers to the slow onset and steadily worsening symptoms of the disease without distinct attacks. There is an accumulation of deficits and disability which may level off at some point or continue over months or years. There is a correlation with time and severity present in patients- whereby the longer the progression, the intensifying of the symptoms,

4. Progressive relapsing

Progressive relapsing is rarely seen in diagnosed MS patient. It refers to the gradual progression of disability from the onset of the disease and is accompanied by one or more relapses.

Outline primary body/organ system/s involved

Central nervous system

 The central nervous system (CNS) consists of the brain and the spinal cord. The brain contains about 85 billion neurons and the spinal cord contains about 100 million neurons (Cooke., etl). The CNS is an extremely important structure within the body as it is the source of emotions and thoughts, as well as involved in the stimulation of muscles to contract and glands to secrete thereby controlling body movements and regulations operation of internal organs.

1. The brain and spinal cord:

The brain can be divided different sections- responsible for different functions.

• The frontal lobe: Located in the forebrain, the frontal lobe is responsible for voluntary movement, participate cognitive tasks
• Parietal lobe: responsible for processing and interpreting somatosensory input and construction of spatial coordinate system
• Temporal lobe: responsible for processing auditory information and with the encoding of memory. It also plays role in processing affect t and language
• Occipital lobe: Responsible for receiving and processing visual information including colour, form and motion
• Medulla oblongata: Regulates breathing and heartbeat, coordinates reflexes swallowing, vomiting, sneezing and coughing
• Cerebellum: Coordinates contractions of the skeletal muscle 
• Cerebral cortex: involved in perception of sensory information. Motor area control execution of voluntary movements

(https://www.health.qld.gov.au/abios/asp/boccipital

1. Neurons:

Neurons of the nervous system (including the PNS and CNS) are responsible for receiving signal, integrating incoming signals and communicate signals to target cells.

As seen in the figure below, the neurons within the CNS are composed of three essential parts: (1) a cell body, (2) dendrites and (3) and axon figure.

https://www.thoughtco.com/neurons-373486

The brain of the CNS is divided into grey matter and white matter. The grey matter is comprised of the dendrites and the neuron cell bodies, whereas the white matter is comprised of the axon cords that extended to and from neurons. The white appearance is due to the myelin fatty insulating sheath surrounding these axons.  This insulating cover allows the nerve consulting signals to travel around the body reliably and quickly.

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Neurons are electrically excitable. They are able to communicate with each other through electrical impulses (action potential) through short or long distances. For instance, in reflex motions, a potential develops in the sensory receptors of the person skin. This potential activates the axon of the sensory receptor to release an electrical impulse to the interneurons of the CNS. The CNS can then analyse and process this information and causing an electrical impulse to motor neuron thereby allowing the neurons to innervate the muscles of your fingers, causing them to let go.

https://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/a/overview-of-neuron-structure-and-function

Incidence and Prevalence and population affected

Worldwide

• Prevalence varies around the world
• More prevalence in woman than in men
• MS has a 10-25 times greater prevalence in individuals of first-degree relatives.
• Peak age 35-45
• Affects approximately 1 % of the population in the United states
• Affects 400,000 people in the United States
• Affects about 100 per 100,000 in the United Kingdom
• MS is twice as common among causations as other races and it is rare among people of Mongolian, Japanese, chines, Native American, Eskimo, African black and Aborigine decent

Australia

• 25,600 people are diagnosed currently with MS
• It is the most common cause of disability in young adults
• On average more than 10 Australian are diagnosed with MS every week

https://multiplesclerosis.net/wp-content/uploads/2013/01/global_2x.png

Presentation

Multiple sclerosis may have a rapid or insidious onset.  It is important to consider that every individual is different and may show difference in severity and symptoms. MS affects a wide range of sensory and motors function of the CNS.

Symptoms:

• Fatigue is one of the most common symptoms found in MS patients. Patients may feel tired and lethargic
• Paraplegia in the extremities or on one side of the face

Muscle weakness, vertigo (faintness or dizziness) and visual disturbances such as nystagmus, diplopia (double vision) and partial blindness.

• Patients in the later course of the disease may experience extreme emotional lability, ataxia, abnormal reflexes and difficulty urinating.
• Bladder dysfunction: may lead to frequent urinary tracts infections (UTI’s)
• Impaired sensation characterised by parenthesis (numbness and tingling)
• Gastrointestinal symptoms including bowel dysfunction, constipation and diarrhea
• Respiratory symptoms including impaired breathing secondary to weakness of respiratory muscles

Signs: The signs of MS are dependent to the site of lesion in the CNS. An individual presenting MS signs include:

• Spasticity of the muscles
• Euphoria (excitement) or depression
• Impaired attentions and memory functions
• Postural deficits and poor articulation

Causes / Aetiology/Risk factors

The aetiology of MS is still debatable, but the current data suggests that environmental factors in genetically susceptible background can predispose an individual to M. Clinical study and research there is a genetic (30%) and environmental (70%) influence that may cause the acquisition on MS.  (Compston and Coles, 2008)

-        Studies show a familial recurrence rate of 20% with first aid degree relative (Compston and Coles, 2008)

Potential risk factors of MS include infections, vaccination, climate and diet. Infections is considered the most common risk factor for MS due to its molecular mimicry proteins found in the CNS causing activated immune cell attack on CNS. In addition, exposure to viral infections including mononucleosis and the Epstein Barr may have an affect (Compston & Coles, 2008; Wakerley et al., 2012

 Other risk factors include latitude, UV light, causation, vitamin D deficiency, obesity, smoking (Hernan, Olek, & Ascherio, 2001) and heavy metal exposure (Noonan et al., 2010)

Progression and prognosis

The clinical course of MS is variable among individuals, however it usually manifests between 20- 40 years old (Wakerley et al., 2012). Life expectancy of individuals diagnosed with MS has increased, whereby they can expect live seven years less than an individual without the disease (national MDS society)

Relapsing- remitting MS

This prognosis is usually not severe as it only involves one or two episodes of neurological deficits with no residual impairments. The chance of remaining symptom free increases with each monosymptomatic year. In other words, the more years, the greater the chance of not being impacted by the disease. No immediate or serious intervention is needed, however change in lifestyle is recommended to alleviate any future attacks.

Progressive MS

The prognosis of an individual with a progressive MS disorder ultimately depends on the severity and worsening of the deficits. Over time, the MS may inhibit many physical functions over the individual which may lead to severe disabling or mortality.   Intervention is highly recommended as it may alleviate the prognosis of the individual.

Ten years after the disease onset, about 10% will be wheelchair bound and about 50% will be unable to work ([Wakerley et al., 2012]). The median time from disease onset to death is around 30 years ([Compston & Coles, 2008]). 

Treatment/Intervention: Common medical interventions and management approaches including surgical, pharmacological, lifestyle and psychological

Surgical intervention is not part of the routine care given for MS.  However, there is strong endorsement towards disease modifying drugs. Drugs such as interferon- B-1b, glatiramer acetate, azathioprine, and fingolimod are particularly useful to help reduce relapses in patients and the progression of MS. ([Carrithers, 2014]; [Harrison, 2014]; [Lyros et al., 2010]; [Wakerley et al., 2012]).

Secondary- line disease treatments are useful in promoting antibodies. These include Alemtuzumab and Natalizumab (Carrithers, 2014)

In addition, future possible treatment of MS includes transplants of Schwann cells or stem cells and antiviral medication wand vaccination ([Noseworthy, 2003]).   Cannabis extract may be used to alleviate pain and in combination with beta blocker to treat spasticity ([Wakerley et al., 2012]). Ant- depressant may be used to treat patient’s affect. Bone marrow transplants are also particularly useful in resetting the immune response and have shown promising effects in reducing relapses

In addition, management strategies such as education, healthy diet, no smoking and exercise are particularly low- impact with gradual increase in intensity and frequency can treat fatigue and be useful in alleviating future MS attacks.

Donepezil, rivastigmine, and galantamine (initially for  Alzheimer’s patients) may improve  cognitive symptoms such as attention, information processing, and memory/learning ([Bobholz & Rao, 2003]; [Lyros et al., 2010]). 

References:

• Melzer N, Meuth SG, Torres-Salazar D, Bittner S, Zozulya AL, Weidenfeller C, et al. (2008) A β-Lactam Antibiotic Dampens Excitotoxic Inflammatory CNS Damage in a Mouse Model of Multiple Sclerosis. PLoS ONE 3(9): e3149. https://doi.org/10.1371/journal.pone.0003149
•  
• Atchison, B & Dirette, D. (2017). Conditions in occupational therapy: effect on occupational performance (5
• th
• ed).
• Philadelphia, Wolters Kluwer/Lippincott Williams & Wilkins.
• Carrithers, M. D. (2014) Update on disease-modifying treatments for multiple sclerosis. Clinical Therapeutics, 36(12),
• 1938-1945
• OTHY103 Pathophysiology for OT                                                               Revised:  Daniel Clohesy ACU 2017
• Atchison, B & Dirette, D. (2017). Conditions in occupational therapy: effect on occupational performance (5th ed). Philadelphia, Wolters Kluwer/Lippincott Williams & Wilkins.
• Carrithers, M. D. (2014) Update on disease-modifying treatments for multiple sclerosis. Clinical Therapeutics, 36(12), 1938-1945

-        Exposure to heavy metals within the environment also may play a role (Noonan et al., 2010)

-        Family history to exposure to viral infections particularly that of mononucleosis and Epstein Barr virus

• (Compston & Coles, 2008; Wakerley et al., 2012)
• Progression and prognosis
• Relapse Remitting MS:
• Is classified as benign as it’s effect is not severe. Its classified as such because one or two ‘episodes’ occur with no
• particular deficits or disabling effects. An individual diagnosed with this type of MS has less probability to retain
• deficits dependent on the amount of non-symptomatic years. (The more years the greater the chance of not being
• severely impacted by the disorder.) Therefore, the individual does not need intense medical intervention, but should
• seek advice from health professionals on partaking in certain life style choices to alleviate any worsening development
• of MS.
• Relapsing Progressive MS:
• Within this diagnosis, the individual will experience MS attacks in which there are no residual effects/deficits due to
• attacks. Individuals diagnosed with this MS should try to alleviate the severity of the attacks within MS by decreasing
• attack onset by making life style choices that reduce risk of attack, for instance quitting smoking.
• Primary Progressive MS:
• Diagnosis of this form of MS is characterised by the worsening of deficits associated with MS. Over time an
• individual’s condition worsens. This type of MS is understood to inhibit many common physiological processes
• meaning that the condition can become very disabling. Intervention within this type of MS is highly recommended as
• to alleviate the severity of the deficits one experiences within their lifetime.
• Treatment/Intervention: Common medical interventions and management approaches including surgical,
• pharmacological, lifestyle and psychological
• There is no surgical intervention within the care of those who have MS.
• In reference to pharmacological treatments certain disease modifying drugs have shown to have positive outcomes
• with reducing particular deficits that are experienced within MS.
• Drugs known to aid MS are:

-        Interferon

• 
• -1b

-        Glatiramer acetate

-        Azathioprine

-        Fingolmod 

-        Have shown some potential in the reduction of relapse and progression of the disease (Carrithers, 2014;

• Harrison, 2014; Lysros et al., 210; Wakerley et al., 2012)
• Second-line disease modifying treatments that promote antibodies within the body are:

-        Natalizuab

-        Rituximab

-        Alemtuzumba

-        (Carrithers, 2014)

• Other experimental medical interventions that could possibly be developed are Schwann cell transplants
• References:
• Atchison, B & Dirette, D. (2017). Conditions in occupational therapy: effect on occupational performance (5
• th
• ed).
• Philadelphia, Wolters Kluwer/Lippincott Williams & Wilkins.
• Carrithers, M. D. (2014) Update on disease-modifying treatments for multiple sclerosis. Clinical Therapeutics, 36(12),
• 1938-1945
• Wakerly, B., Nicholas, R., & Malik, O. (2012). Multiple Sclerosis. Medicine, 40 (10), 523 – 528.
• Compston, A., Coles, A. (2008). Multiple Sclerosis. Lancet, 359, 1500-1520

• Compston, A., Coles, A. (2008). Multiple Sclerosis. Lancet, 359, 1502-1517
• Kuhlmann, T., Lingfeld, G., Bitsch, A., Schuchardt, J., & Brück, W. (2002). Acute axonal damage in multiple sclerosis
• is most extensive in early disease stages and decreases over time. Brain, 125(10), 2202-2212.
• Wakerly, B., Nicholas, R., & Malik, O. (2012). Multiple Sclerosis. Medicine, 40 (10), 523 – 528.

• u.au/brain/brain-anatomy/central-nervous-system-brain-and-spinal-cord