MS Multiple Sclerosis

Definition/Description

Multiple sclerosis (MS) is an autoimmune disorder characterized by inflammation,selective demyelination and gliosis[1] causing both acute and chronic symptoms and resulting into significant disability and impaired quality of life. MS affects An inflammatory response occurs when the body's immune cells attack the CNS (often referred to as an exacerbation or relapse) which leads to an increase in pressure thereby disrupting nerve conductivity. Demyelination is a process, where myelin is damaged, due to the autoimmune response,leading to decreased nerve conduction velocity and early fatigue of the nerve. Gliosis occurs when demyelinated areas become fibrotic,causing proliferation of neuroglial tissue and scarring in the CNS. [1] 
Subtypes. Image provided by GetThePapersGetThePapers with permission Creative Commons Image provided by GetThePapersGetThePapers with permission Creative Commons

The course that MS can take will be different from one person to another as well as unpredictable.The disease can be divided into four clinical subytpes,which describes how the disease will progress as well as the corresponding characteristics that become evident for each subtype:

  • Relapsing-remitting MS (RRMS) is the most commone subtype, affecting 85% of people with MS and is characterized by short attacks to the CNS followed by complete or partial return to normal functioning[1].
  • Secondary-progressive MS (SPMS) is a subgroup that begins as a relapsing-remitting course accompanied by a steady decline in function and is often developed by patient.
  • Primary-Progressive MS (PPMS) is a progression of the disease where a steady decline in function experienced from the onset of the disease.
  • Progressive-Relapsing MS (PRMS) is similar to PPMS but has the additional characteristic of acute attacks.


Prevalence

It is estimated that in the United States there are 400,000 people being affected by MS and 2.1 million people globally[1]. Females are 2 to 3 times more likely to have MS than males, which may indicate hormones play a role in acquiring the disease.[2] The prevalence of MS has increased within the last 5 decades with the increase primarily being due to females[1]. MS rarely occurs in children as well as adults over the age of 50 and will most commonly present between the ages of 20-40 years.[1] The risk of being diagnosed with MS is increased in a person, who has a sibling with MS by 3%, a fraternal twin by 5% and an identical twin by 25%.[1] 

MS can occur in many ethnics groups, with the most common populations being Caucasians with an ancestry from northern Europe, followed by African-Americans, Latinos/Hispanics and Asians[2]. It is rarely seen in ethnic populations such as, Australian Aborigines, New-Zealanders, Yakutes, Inuit, Hungarian Romani and Norwegian Lapps[2]. There have been studies that show the prevalence of MS is higher in some geographical locations than in others, such as northern United States, norther Europe, southern Canada, New Zealand, Southern Australia and Scandinavian countries. Regions with a lower prevalence of MS tend to be closer to the equator, such as Asia, Africa, and South America[1].

Worldwide Prevalence. Image provided by derivative works from Gabby8228, Faigl.ladislav, and Dekoder with permission Creative Commons

Etiology/Causes

The cause of MS is still unknown but there have been studies that show the interaction of several different factors, which could play a role in the etiology.

Immunologic factor: The body's own immune cells attack the CNS and ultimately destroy nerve conduction[2]. Researchers have been able to identify what immune cells are attacking the CNS, the cause for their attack and some of the receptors on the attacking cells that make them attracted to myelin[2].The T cells (one type of white blood cell in the immune system) somehow become sensitized to proteins in the CNS. When T cells become activated, they enter the CNS through blood vessels and produce damaging inflammation. Once in the CNS, these T cells not only injure myelin, but also secrete chemicals that damage nerve fibers (axons) and recruit more damaging immune cells to the site of inflammation. It is not known what causes T cells in persons with MS to become activated but it is postulated that both genetic and environmental factors are important.[3]

Environmental factor: MS appears to be more prevalent in areas farther from the equator in a colder climate. There is some evidence that shows Vitamin D may play an important role in that people who live in a warmer climate are exposed to the sun more and therefore their body naturally produces more Vitamin D.It is thought that larger amounts of naturally-produced Vitamin D may increase immune function and protect the body against autoimmune diseases[2].

Genetic factor: The risk of MS increases in a person who has a first degree family member with the disease, however MS is not considered to be hereditary. Studies have shown that in populations with higher rates of MS as well as in families where several members have MS there are similar genetic factors.The common genetic factors are continuing to be studied in the role they play for developing MS.[2]

Infectious factor: There is a possibility that viruses and other infectious agents may trigger the onset of MS. Many viral and bacterial infections are being investigated.Study [4] suggests possibility of virus or virus triggered immunopathology in MS,suggesting virus reactivating after years of latency.Argument of viral cause is supported by the presence of oligoclonal bands in brain and cerebrospinal fluid,which persists throughout the lifetime.The presence of oligoclonal bands are found exclusively in infectious CNS disorders.The contribution of Epstein Barr virus to the cause of MS is not yet established, but a relationship is clearly present.[5][6]

Gut microbiome factor: It is hypothesized that, gastrointestinal microbiota might play an important role in pathogenesis of MS.Recent evidence suggests that, gut microbiota is one of the key environmental factors.[7] According to the“hygiene hypothesis”, reduced exposure to infections in childhood may increase the risk of allergic and autoimmune diseases.Supporting this argument,western societies report an increased incidence of diseases with an autoimmune/allergic component, including MS.Increased constipation,fecal incontinence,increased gut permeability and increased occurrence of inflammatory bowel diseases in MS patients and their families,suggest an important gut–CNS connection. Interestingly, gut bacteria can also influence the blood brain barrier integrity.However research says,it is difficult to say with certainty whether, changes in gut microbiota is a cause or consequence of MS because MS patients have immunological and microbial changes months to years before clinical onset of the disease.So further research is needed to determine a role of gut microbiota and their metabolites in the susceptibility to and protection from MS.[8]

Mechanisms of Multiple Sclerosis[9]
Feature Disease Mechanism
Autoimmunity MS is a cell-mediated autoimmune disease directed against CNS myelin antigens that involves both CD4+ and CD8+ cells. Autoantibodies may play a secondary or enhancing role. Autoreactive T cells against myelin components exist in normal individuals and, in these individuals, do not cause disease and may even have brain-protecting properties. MS is induced when pathogenic Th17- and Th1-type and CD8 myelin autoreactive T cells are induced.
Infection Infectious agents play a crucial role in inducing myelin-reactive pathogenic T cells. Potential mechanisms include cross reactivity with CNS myelin antigens, triggering an already expanded autoreactive immune repertoire or a self-limited infection of the brain that releases myelin antigens. MS is not caused by a persistent viral infection of the brain or transmissible agent.
Genetics Both MHC and non-MHC genes are risk factors for development of MS. MHC genes determine immune repertoire whereas non-MHC genes determine regulatory and tolerance mechanisms in MS, both of which are defective.
Environment Environmental factors can increase the risk for both the development of MS and the disease course and include lowered vitamin D, lowered UV radiation exposure, cigarette smoking, obesity, and EBV exposure.
B cells B cells play a central role in MS. Like T cells, there are pro- and anti-inflammatory B cell subsets. In relapsing MS, B cells serve as primary antigen-presenting cells that drive pathogenic T cells. In progressive MS, B cells enhance the compartmentalized CNS responses through lymphoid follicles and secreted factors.
Microbiome The microbiome regulates T cell function throughout the body and contains both protective and pathogenic microbial components, which play an important role in MS by establishing immune set points and by secreting metabolites.
Relapsing MS Relapsing MS is driven by immune cells that migrate into the CNS. Multiple treatments have been shown to effectively treat relapsing MS (decrease relapses and new MRI lesions) and act on the following common pathways: decrease number and/or function of effector cells, increase number and/or function of regulatory cells, and prevent trafficking of cells to the CNS.
Progressive MS Progressive MS mechanisms include those that are immune dependent and immune independent. In immune-dependent forms, an innate immune response is established in the brain that involves microglia, macrophages, B cells, and lymphoid follicles. There may also be chronic activation of peripheral T cells and innate cells. In immune-independent forms, mitochondrial injury, oxidative stress, and ion imbalance occur. Current therapy does not effectively target these two processes.
Autoantigen The inciting autoantigen in MS is unknown. However, when MS is diagnosed, there would be no single autoantigen to target as there is spreading of reactivity to other organ-specific antigens as occurs in type 1 diabetes. Thus, antigen-specific therapy would have to employ bystander suppression or be given as a preventative strategy in at risk subjects.
Therapy MS is a heterogeneous disease. There will be responders and non-responders to each “effective” therapy. The earlier in the disease course that treatment is initiated, the more likely it is to be effective. Effective treatment will require pulse or continuous therapy and, ultimately, combination therapy. The identification of immune and MRI biomarkers will be the cornerstone of immunotherapy of MS and the achievement of no evidence of disease activity (NEDA).

Characteristics/Clinical Presentation

Multiple Sclerosis will present with varying symptoms depending upon the location of the nerves being affected[1]. Symptoms usually appear suddenly and rapidly over a period of minutes or hours,but in more rare cases the symptoms may be insidious and take several weeks to months to develop[1].

Early symptoms:-

  • Numbness and weakness in one or several limbs progressing from parathesias,
  • Visual disturbances such as double vision and
  • Fatigue are typically the early symptoms that will present with MS[1].

Other common symptoms presented with MS are[1]:

  • Pain: Headache, chronic neuropathic pain, paroxysmal limb pain.
  • Cognitive symptoms: Short-term memory deficits, diminished executive function, diminished attention/concentration.
  • Affective Symptoms: Depression, anxiety.
  • Motor symptoms: spasticity, spasms, ataxia, impaired balance and gait.
  • Speech and swallowing: dysarthria, dysphonia, dysphagia.
  • Bladder/Bowel symptoms: spastic or flaccid bladder, constipation, diarrhea and incontinence.
  • Sexual Symptoms: impotence, decreased libido, decreased ability to achieve orgasm.

The pattern of symptoms will be different from person to person.The initial symptoms are typically acute and followed by a period of remission with complete or partial recovery[10]. An increase in symptoms can occur with an increase in body temperature because many MS patients have a sensitivity to heat[10]. Multiple sclerosis can also cause lumbar radiculopathy.

The disease is the most common cause of neurological disability affecting people in their productive years, between 15 and 55 years of age. [11] It afflicts women more often than men (ratio of approximately 2:1).[12] Overall course and prognosis in multiple sclerosis is most likely to be related to age and the occurrence of the progressive phase of the disease, rather than to relapses or other clinical parameters. Individual prognosis remains hazardous.[13]

Associated Co-morbidities

Co-morbidities are common among the aging population especially with added risk factors of a poor diet and obesity.They often lead to a decrease in functional status and quality of life. Knowing the prevalence and common types that exist in MS,can help with disease management, to maximize an individual’s overall physical well-being. Common co-morbidities seen in patients with MS include [14]:
Autoimmune
• Inflammatory bowel disease
• Thyroid disease
• Uveitis
• Arthritis
• Systemic lupus erythematosus

Physical
• Hypertension
• Hyperlipidemia
• Heart disease
• Cancer
• Chronic lung disease

• Osteopenia/Osteoporosis

Behavioral
• Anxiety
• Depression
• Sleep disorders
• Alcohol use
• Obesity

Other less common co-morbid conditions include: kidney disease, asthma, cancer, Sjogren’s syndrome, and liver disease.

Systemic Involvement

Nervous System: MS greatly impacts the CNS system when the body's own immune cells attack the myelin, which exposes the nerve and creates a disconnect between the brain and the rest of the body. The disruption between the brain and the body creates a decrease in function throughout the body[15]. MS impacts the brain with symptoms such as, memory loss, confusion, dizziness, vertigo, personality changes, depression and less commonly, seizures[15].

Vestibular System: Vision disturbances are a common first symptom with MS that come on suddenly in one or both eyes[15]. Symptoms may present as blurred or double vision, pain, and trouble seeing contrast in one or both eyes[15]. Vision impairments are due to inflammation and fatigue to the eye muscles and are temporary in most cases. Hearing loss is another affect of MS but less common to occur[15]. Problems with hearing usually occur due to damage to the brainstem and most commonly resolve on their own[15].

Affected systems. Image provided by Mikael Häggström with permission Creative Commons

Pulmonary System:
Decreased function of the respiratory muscles due to nerve damage can create speech as well as breathing difficulties. This complication usually occurs early on in the disease process and worsens as MS progresses[15]. Swallowing difficulties can also arise because the muscles responsible for swallowing become weak due to nerve damage. Problems with swallowing can lead to food or liquid to get into the lungs and cause an infection[15].


Musculoskeletal System:
Muscle weakness, numbness and tingling are common symptoms to occur because of demyelination in MS. This complication can lead to problems such as decreased hand-eye coordination, balance, gait, and fine motor skills because the brain has difficulty sending information to the nerves and muscles[15]. As the disease progresses these symptoms may worsen and make assistive devices necessary for gait and mobility. MS can also increase the risk of bone fractures and osteoporosis because of steroid use and inactivity, which decrease bone density[15].


Autonomic System:
MS can affect the bladder when damage to the nerves that control bladder and sphincter function occurs[2]. The bladder can become “spastic” in which it is unable to empty urine properly or a “flaccid” bladder in which it is unable to hold urine[2]. Bowel problems are another complication that can occur in MS patients and will present as a loss of bowel control as well as constipation. Sexual impairments is a common occurrence in people with MS, which occurs when the nerves sending information to the sexual organs are damaged[2]. This damage can lead to problems in arousal and orgasm. Sexual impairments can also be caused by other MS symptoms, such as fatigue, spasticity and mood[2].


Integumentary System:
MS patients are at a much greater risk of skin break down due to sensation loss, heat sensitivity, muscle weakness/paralysis and immobility[1].


Diagnostic Tests/Lab Tests/Lab Values

Multiple Sclerosis is diagnosed by a neurologist by performing a detailed medical history, neurological exam as well as ordering supportive laboratory tests. The laboratory tests are used to diagnose as well as rule out other possible conditions that may present similarly[10].

Magnetic Resonance Imaging (MRI):

An MRI is very sensitive in detecting  MS plaques that are found in the white matter of the brain and spinal cord[1]. The plaques that appear on the MRI may also be seen with conditions, such as Lupus, diabetes as well as migraines and therefore cannot be used to give difinitive reasoning to rule in MS[10].

Monthly MRI changes over 1 year. Image provided by Waglione with permission Creative Commons

Spinal Tap (Lumbar Puncture):

A spinal tap is a procedure in which a needle is inserted into the lumbar spine to remove a small amount of cerebral spinal fluid, which is then brought to a lab for analysis[10]. The cerebral spinal fluid is tested for abnormal amount of white blood cells, proteins and other abnormalities that are secondary to MS.[10]

Evoked Potential Test:

The evoked potential test measures electrical signals in the nerves sent from the brain in response to a stimuli.[10] The stimulus may be visual or electrical in origin[10]. This test helps detect whether there is a lesion to a nerve in the optic nerve, brainstem and spinal cord even though a person may not be presenting with any neurological signs of nerve damage[10].

Blood Tests:

A blood test is beneficial to perform to rule out other conditions that may present similar to MS, such as infectious or inflammatory diseases[10].

Differential Diagnosis

Diagnosis of MS can be a complicated task. An easy mnemonic to aid in differential diagnosis used by the National Multiple Sclerosis Society is VITAMINS:[2]

 Vascular: Multiple lacunar infarcts; CADASIL; spinal arteriovenous malformation

 Infectious: Lyme disease; syphilis; HIV myelopathy; PML; HTLV-1 myelopathy

 Traumatic: Spondylitic myelopathy

 Autoimmune: NMO; acute disseminated encephalomyelitis; CNS vasculitis; Behcet syndrome, sarcoidosis; SLE

 Metabolic/Toxic: Central pontine myelinolysis; vitamin B12 deficiency; vitamin B6 deficiency; radiation; hypoxia

 Idiopathic/Genetic: Spinocerebellar degeneration; Friedreich ataxia; Arnold-Chiari malformation; adrenoleukodystrophy; metachromatic dystrophy

 Neoplastic: CNS lymphoma; glioma; paraneoplastic encephalomyelitis; metastatic cord compression

pSychiatric: Conversion disorder.

Medical Management

Acute Relapse Managment: work as immunosuppressents and anti-inflammatory drugs to reduce CNS swelling.There are numerous medications available in assisting acute attacks, disease progression, and to help manage symptoms [2].

 Prednisone:   Typically, a high dose of a corticosteroid, such as methylprednisolone, is the first line of treatment against an attack of MS[16][10]. Corticosteriods help to reduce and inflammation by suppressing the immune system, and when given intravenously can work quickly [16]. Oral doses are often given as follow-up treatments during acute exacerbations [16]. Side effects include sleep disturbance, headache, excessive sweating, or increased hair growth[2]. Prolonged corticosteroid use can also lead to skin problems, edema of face or lower extremities, arthralgias, irregular menstration, muscle cramps, and pain[2]. Brand Name: Deltasone[2]

 
Plasmapheresis: As a supplemental or secondary treatment, plasmapheresis (plasma exchange) can be used in relapsing forms of MS to help control MS attacks [16]. During the plasmapheresis procedure potentially harmful components of plasma are separated and removed from blood, then replacement plasma and blood cells are returned to the body [16] This method is thought to be useful as a secondary treatment option for severe relapsing forms of MS, but is not recommended for PPMS or SPMS[2].

Disease-Modifying Agents: work to slow progress or reduce the number of MS attacks:They are most commonly used for decreasing relapses in patients with RRMS [16]. Prior to initiating disease-modifying treatment, a complete diagnostic work-up is crucial to help begin treatment at the appropriate time. Early intervention using disease-modifying drugs has been shown to be most effective however, the risks involved in prematurely starting treatment for MS if this is not the true diagnosis can cause an individual to become susceptible to the serious side effects of taking some of these drugs [16]. The following disease-modifying drugs work to slow progress or reduce the number of MS attacks.
Beta Interferons.

Interferon work to reduce the number of attacks and lessen the severity of MS attacks during early stages of RRMS [16].

Common side effects include reaction to injection site, liver damage, fever, chills, muscle pains, or fatigue[10][16]. Following the first 18-24 months some patients may develop antibodies that can dampen the interferons effect, so physicians may turn towards alternative disease-modifying agents [16].Brand Names: Avonex, Betaseron, Extavia, and Rebif[10]

Glatiramer acetate.

Injectable disease-modifying drugs that may help alter immune cells from attacking myelin[10]. The exact mechanism of action is not entirely understood[2].

Mild side effects include injection site irritation or allergic reactions; more rare side effects include flushing, anxiety, chest pain, or heart palpitations[2].Brand Name: Copaxone[2]

Mitoxantrone.

Injectable drug given four times per year that suppresses immune functions thought to attack myelin[16]. This drug is approved for treating SPMS, PRMS, and RRMS[2].

In a small percentage (~1%) this drug has been correlated with some types of blood cancers and can be harmful the heart[16]. Consequently, prior to receiving this medication patients should receive periodic check-ups with their doctor regarding heart function as well as other medical issues such as chicken pox, shingles, gout, kidney or liver disease[2].

Side effects range from nausea, hair loss, irregular menses to more serious side effects such as, lower extremity swelling, cough, shortness of breath, low back pain, tarry stools, or sores around mouth [2].Brand Name: Novantrone[2]

Natalizumab.

This drug is given monthly by intravenous infusion and works by preventing possibly damaging immune cells from entering the brain or spinal cord[2]. The drug is approved for treating relapsing forms of MS, especially in those that are not responding to other treatments[2].

However, those taking Natalizumab are at an increased risk for developing progressive multifocal leukoencephalopathy (PML), a viral infection that can be fatal[2]. Side effects include headache, fatigue, depression, diarrhea, abdominal pain, UTI and GI distress.Brand Name: Tysabri[2]

• Fingolimod.

A new drug that is the first MS daily oral treatment for those with RRMS[2]. The disease-modifying agent works by preventing specific lymphocytes from exiting lymph nodes and entering the central nervous system (CNS)[16]. The first dose should be taken under the supervision of a physician due to an increased risk of bradycardia (heart rate <60bpm) or other heart issues, and eye problems such as uveitis[2][16].Side effects include headache, influenza, diarrhea, back pain, abnormal liver tests, and cough[2].Brand Name: Gilenya[2]

Symptom management

It is an integral component to helping patients with MS function in their daily life. Numerous pharmacological agents can be used to relieve common symptoms of MS.

Spasticity is best treated on an individual basis. The most common treatments include muscle relaxants such as baclofen or tizanidine (Zanaflex)[1]. Other medications include diazepam (Valium), dantrolene (Dantrium), phenol, or botulinum toxin (Botox)[2].  

Pain is a common symptom present in MS and can present acutely or as chronic pain [1].

o Acute Pain Treatment
- Trigeminal neuralgia—stab-like facial pain with anticonvulsants
            • Carbamazepine (Tegretol) or phenytoin (Dilantin)[1][2]
- Lhermitte’s sign—stabbing, electric-shock pain along the back that is elicited with neck flexion treated with anticonvulsants[2]
- Dysesthesias—burning, aching neurological pain can be treated with anticonvulsant or antidepressant medications[2]
            • Amitriptyline (Elavil), imipramine (Tofranil), gabapentin (Neurontin), desipramine (Norpramin)[1][2]
- Paroxysmal Pain—sudden sharp pains that will respond to:
            • Carbamazepine (Tegretol), amitriptyline (Elavil), phenytoin (Dilantin), diazepam (Valium), or gabapentin (Neurontin)[1]
   

o Chronic Pain Treatment
 - Burning, aching, “Pins & Needles—treated the similar to acute dysesthesias[2]
            • Gabapentin (Neurontin), amitriptyline (Elavil)[2]
- Spasticity—muscle spasm medications range from over-the-counter to prescription anti-inflammatory drugs[1]
            • acetaminophen, ibuprofen, baclofen (Lioresal), tizanidine (Zanaflex)[1][2]

Fatigue is an extremely prevalent symptom and the cause can often be due to comorbid conditions such as depression, thyroid disease, anemia, or as a side effect of another medication already prescribe to a patient with MS[2]--amantadine hydrochloride (Symmetrel), modafinil (Provigil)[1][2]

Tremor can present in varying degrees in different forms (intention, postural, resting, nystamgus) consequently, treatment response is also variable[1].--hydroxyzine (Atarax, Vistaril), clonazepam (Klonopin), propranolol (Inderal), buspirone (Buspar), ondansetron (Zofran), primidone (Myosline), or meclizine (Antivert)[1][2]

Cognitive & Emotional Impairments often seen in patients with MS include depression and memory deficits.
o Depression management includes antidepressant medications such as fluoxetine (Prozac), Paxil, sertraline (Zoloft), and amitriptyline (Elavil). Professional counseling and support groups are also encouraged[1].
o Memory deficit management has used donepezil (Aricept), a drug often used for the treatment of Alzheimer’s disease[1].

Bowel & Bladder Impairments differ according to whether the issue is with storing to expelling contents[1].
o Bladder storage dysfunction (overactive, spastic bladder) is treated with anticholinergics (propantheline (Pro-Banthine), oxybutynin (Ditropan), imipramine (Tofranil)[1]. o Bladder emptying dysfunction (flaccid bladder) is treated with alternative emptying techniques such as the Crede maneuver or intermittent self-catheterization[1].
o Dyssynergic bladder (combined dysfunction) is treated with alpha-adrenergic blocking like agents terazosin (Hytrin), prazosin (Minipress), tamsulosin (Flomax) & antispasticity agents such as baclofen[1].
o Constipation is treated through diet and bulk-forming supplements such as Metamucil, FiberCon, Citrucel, Benefiber or stool softeners[1].

For more information and drug listings on symptom management, please visit the following link:

www.nationalmssociety.org/Treating-MS/Medications

Physical Therapy Management (current best evidence)

Physical therapy can play an essential role in keeping a patient with MS active and functional within the community.While there is no cure for multiple sclerosis, exercise appears to be beneficial at multiple levels and it may have an important role to play in delaying negative symptoms of the disease. Exercises should be chosen according to one's strengths and weaknesses [17](LOE:1A). It is suggested that exercise therapy does have efficacy in MS.It is to state the best ’dose’ (intensity, frequency and duration) of treatment to achieve optimal beneficial effects of exercise therapy in terms of activities and participation for patients suffering from MS. There was no evidence describing harmful effects of exercise therapy for MS patients. [18] (LOE: 1A).Exercise is consider as a safe effective means of rehabilitation.[19]

The PT assessment should focus on posture, movement and function, carefully considering how a patient's performance may be limited by fatigue, pain or other factors. Analyzing these results together with the proper opinion and interest of the person with MS will enable the physiotherapist to set up an individualized program. This program needs to be set up so that it can easily be performed at home.Education is also important to assist patients in managing their programs as independently as possible. A multidisciplinary treatment for MS patients may lead to positive effects.[13]( LOE: 1C).

During early stages of MS patients may present with minimal impairments. At this time, the PT can focus on educating the patient and family members or caregivers on disease progression and compensatory strategies to conserve energy[1](level of evidence:5)[20](LOE: 1C).Physiotherapist,should emphasize movement outdoors especially in sunlight in order to avail the direct benefits of sunlight in MS.The recent study suggests life time sun exposure appears to reduce the risk of Multiple Sclerosis regardless of race/ethnicity. Study indicates the protective effect of sun exposure in MS is most likely mediated through immunomodulatory mechanisms, [21]

Due to the progressive nature of the disease, those in the moderate stage might notice impairments at varying degrees and activities of daily living (ADL) may require assistance. At this middle stage,therapy should focus more on improving or maintaining motor functions through strength, endurance, flexibility, balance, respiratory training and assistive device training as well as suggesting environment modifications to the home or assessing mobility aids required to move about in the community to sustain quality of life[1](LOE: 5)[20](LOE:1C). Informing the carers about correct postures will prevent further complications. A close collaboration between professional community carers and non-professional caregivers at home is a key factor for the successful management of the rehabilitation. [22](LOE:1C)

Advanced stages of MS often present with multiple impairments at increasing severity compared to earlier stages. The primary goals of the PT in late stages is to maximize independence through postural and ADL training, respiratory function, safety and prevention strategies for contracture development or pressure wounds, equipment suggestions, and proper transfer techniques[1](LOE:5)[20](LOE:1C)(5)(LOE: 2A).

  • Physiotherapy treatments -active/passive/active assisted exercises(carried with partner or with help of equipment like elastic bands);techniques like Bobath,Vojtas,Proprioceptive Neuromuscular Techniques; carried out regularly and with sufficient intensity, have evidence of improvement in patients with MS.[23]
  • Use of therapeutic corticosteriods and inactivity due to fatigue and weakness,may lead to osteoporosis and pathological fractures.Weight bearing exercises can slow down the loss of bone and muscle mass. Resistance training program is recommended for maintaining bone and muscle mass,[19]
  • According to Döring et al. aerobic training seems to have a positive effect on fatigue.[24]Aerobic exercise training with low to moderate intensity can result in the improvement of aerobic fitness and reduction of fatigue in MS patients,affected with mild or moderate disability[25]
  • Specific balance exercises can improve balance.Poor postural control increases risk of falls.MS patients have increased sway in quiet stance,delayed postural perturbations and reduced ability to move towards limits of stability.These impairments are likely causes of falls.Reduced gait speed,decreased stride length, cadence,and joint movement are observed in most studies of gait in MS.[26] The therapist must identify several factors that may be amenable to intervention to prevent falls in people with MS.Comprehensive exercise interventions can facilitate improvements in balance impairments.Functional balance exercises can positively impact balance, physical activity and quality of life in adults with multiple sclerosis [27]
  • Motor Imagery is increasingly used in neuro-rehabilitation in-order to facilitate motor performance.Motor imagery and rhythmic auditory stimulation can be used for walking rehabilitation in MS patients.[28].Randomized controlled trial studying the effects of motor imagery showed significant improvement in walking speed,walking distance,perception and quality of living.[29]
  • Hippotherapy has a positive effect on balance of persons with multiple sclerosis and has an added benefit of enhancing quality of life. [30](LOE:1A).A systematic review and meta-analysis of therapeutic effect of Horseback riding intervention shows positive physical and emotional effects of horse riding in individuals with neuromotor development and physical disabilities.[31] Therapeutic horseback riding improved balance and gait of ambulatory patients with MS.[32] Hippotherapy helps the rider,by providing effective sensory stimulation and rhythmic anterior and posterior swinging motion.It encourages the rider to achieve proper posture and balance.[33]
  • Aquatic exercise program could have a positive effect for persons with progressive multiple sclerosis. Interventions that promote general health, improve energy levels and mental health, and faster social interaction in the presence of physical disability are beneficial for individuals with progressive multiple sclerosis. [34](LOE:1C). Because of reduced impact of gravity, aquatic training allows patients with even severe paresis of the lower extremities to perform standing and moving exercises.
  • In MS patients, beneficial effects of regular physical activity and exercise on mood and quality of life have been repeatedly reported.Valid data on the effect on cognitive function are hardly available. [24] (LOE: 1A). Cognitive Behavioral Therapy (CBT) ]have a moderately positive effect on fatigue in MS. However,this effect declines after cessation of treatment. Since the short-term effect of CBT on MS-related fatigue is positive, there is a need for more research, to develop interventions that, maintain these short-term effects in the long term.To have good results, it is best that the patient should be referred to a CBT specialist.[35] (LOE: 1A) [36] (LOE: 2B). CBT can also be an effective intervention for reducing moderate depression, over a short-term, in MS patients,which may also improve patient quality of life.[37] (LOE: 1A)

Throughout all stages of MS,PT can offer psychological support to the patient and family/caregiver.[1](LOE:5).

PT Interventions for Common Symptoms of Patients with MS:

  • Pain. Patients with MS often experience pain directly from the disease, secondary to medication or other symptoms, or from something completely separate. PT helps relieve pain through exercise, stretching, massage, ultrasound, postural training, or hydrotherapy.[1] (LOE : 5)
  • Sensory Deficits. Tapping and verbal cues during exercise and resistance training can help improve proprioception losses. Vision issues, such as blurred or double vision, often occur in patients with MS. PT can offer education on how to be safe at home and offer strategies to improve balance and coordination in dimly lit settings. PT treatment interventions for decreased sensation to light touch include education on awareness, protection, and personal care to desensitized body parts. Pressure-relieving devices are a primary prevention strategy along with proper transfer techniques and daily skin inspections for maintaining skin integrity.[1] (LOE : 5)
  • Fatigue. One of the most debilitating symptoms of MS is experienced by an overwhelming majority of patients: fatigue. PT strategies to help patients combat feelings of excessive tiredness include aerobic exercise, energy conservation, and activity pacing. Aerobic exercise activities is closely monitored by a PT to ensure a patient does not overheat, but is able to work on increasing their endurance capacity which will help them be more functional throughout the day. PT’s can also teach energy conservation strategies and activity pacing to help someone sustain their daily activities by minimizing fatigue.[1] (LOE : 5)
  • Spasticity. The physical and functional limitations spasticity leads to include include a variety of impariments which can present as contractures, postural deformities, decubitus ulcers, and more. PT interventions range from cryotherapy and hydrotherapy to therapeutic exercise, stretching, range of motion activities, postural training, and electrical stimulation. A combination of therapeutic interventions is often the route taken.[1] (LOE : 5)
  • Balance, Coordination, & Postural Deficits. Ataxia, postural instability, muscle spasms, and generalized muscle weakness al contribute to balance and coordination deficits. PT techniques to address these issues include postural exercise, core strengthening, rhythmic stabilization, static/dynamic balance training, aquatic therapy, proprioceptive loading, and resistance training.[1] (LOE : 5)
  • Mobility Issues. Weakness, particularly in the lower extremity, balance deficits, fatigue, posture, contractures, sensation deficits, heat intolerance, among other deficits, can impede an individual's ability to be mobile. In combination of the treatment previously described, PT's work to help patient's overcome their mobility limitations through locomotor and functional training. Locomotor training focuses on increasing thigh and hip strength along with posture and balance training through walking activities. Orthotics and assistive devices are added as necessary. Functional training involves bed mobility, transfers, and developing strategies with the patient on how to be able to safely navigate around the home and out in the community.[1] (LOE : 5)

Dietary modification

Diet plays a huge role in health.Research suggests adding inflammatory fighting foods to diet can help in chronic inflammation.[38][39]

Number of factors may be thought to play role in triggering inflammation- gluten and dairy products[40],vitamin D deficiency.Diet rich in whole fresh foods and eliminating dairy,sugar,high salt and processed food is highly recommended.

Many researchers are exploring dietary intervention approaches in MS to improve lifestyle[39]. Probiotics[41] may improve the health of people with MS by reducing disability and improving inflammatory and metabolic parameters[42]according to an Iranian study.

Vitamin D supplementation helps prevention and treatment of MS.[43] Various research studies are studying the effectiveness of vitamin D therapy in MS. [44]

Fish oil supplementation given together with vitamins and dietary advice can improve clinical outcome in patients with newly diagnosed MS.[45]More research is required to assess the effectiveness of dietary interventions of omega 3 in MS and it's interaction with medications used for treating MS.[46][47]

Dysfunction of mitochondria is thought to play an important role in mechanism of progression of demyelinating disorders.[48]Observations in animal and histopathological studies,suggest that,dysfunctional mitochondria are important contributors to damage and loss of both axons and neurons.[49] The relationship between mitochondrial dysfunction and neurodegeneration in MS is explored.The Ketogenic diet has the potential to treat the neurodegenerative component of progressive MS,though more research is required in this field.[50][39]

http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Documents/Diet-and-Multiple-Sclerosis-Bhargava-06-26-15.pdf

http://multiple-sclerosis-research.blogspot.com/2016/05/clinicspeak-intermittent-fasting.html

Case Reports/ Case Studies

Community physiotherapy and continence nurse specialist management of a woman with multiple sclerosis and urinary incontinence: a case study

Exploring Barriers to Remaining Physically Active: A Case Report of a Person with Multiple Sclerosis 

Cervical Disk Pathology in Patients With Multiple Sclerosis: Two Case Reports 
Endurance Training in Patients With Multiple Sclerosis: Five Case Studies 

Resources

MS Ireland

National Multiple Sclerosis Society
Multiple Sclerosis Association of America

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 1.33 1.34 1.35 1.36 1.37 1.38 1.39 1.40 O'Sullivan S, Schmitz T, Fulk G: Physical Rehabilitation. 6th edition. Philadelphia, PA. F.A. Davis Company; 2014. (LOE: 5)
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 2.30 2.31 2.32 2.33 2.34 2.35 2.36 2.37 2.38 2.39 2.40 2.41 2.42 National Multiple Sclerosis Society. Incidence and Prevalence of MS. http://www.nationalmssociety.org/What-is-MS/Who-Gets-MS. (Accessed: 21 March 2014)
  3. https://www.nationalmssociety.org/What-is-MS/Definition-of-MS/Immune-mediated-disease
  4. Owens GP, Gilden D, Burgoon MP, Yu X, Bennett JL. Viruses and multiple sclerosis.https://www.ncbi.nlm.nih.gov/pubmed/22130640 The Neuroscientist. 2011 Dec;17(6):659-76.
  5. Tselis A. Epstein–Barr virus cause of multiple sclerosis. https://www.ncbi.nlm.nih.gov/pubmed/22617821Current opinion in rheumatology. 2012 Jul 1;24(4):424-8.
  6. Fernández-Menéndez S, Fernández-Morán M, Fernández-Vega I, Pérez-Álvarez A, Villafani-Echazú J. Epstein–Barr virus and multiple sclerosis. From evidence to therapeutic strategies. https://www.ncbi.nlm.nih.gov/pubmed/26810546Journal of the neurological sciences. 2016 Feb 15;361:213-9.
  7. Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Soldan MM, Luckey DH, Marietta EV, Jeraldo PR, Chen X, Weinshenker BG.https://www.nature.com/articles/srep28484 Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Scientific reports. 2016 Jun 27;6:28484.
  8. Shahi SK, Freedman SN, Mangalam AK. Gut microbiome in multiple sclerosis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730390/The players involved and the roles they play. Gut microbes. 2017 Aug 2;6:1-9.
  9. Baecher-Allan C, Kaskow BJ, Weiner HL. Multiple Sclerosis: Mechanisms and Immunotherapy. Neuron. 2018 Feb 21;97(4):742-68.https://www.ncbi.nlm.nih.gov/pubmed/29470968
  10. 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 10.13 Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269Disease and Conditions Multiple Sclerosis
  11. European-wide recommendations on rehabilitation for people affected by multiple sclerosis; EMSP and R.I.MS; October 2004(LOE: 2A)
  12. Sean Horton, Dany J. MacDonald, Karl Erickson; MS, exercise, and the potential for older adults.fckLREur Rev Aging Phys Act. 2010; 7:49–57 (LOE: 1A)
  13. 13.0 13.1 Sandra Vukusica and Christian Confavreux.; Natural history of multiple sclerosis: risk factors and prognostic indicators.; Current Opinion in Neurology. 2007; 20:269–274(LOE:1A)
  14. Miller, A. Multiple Sclerosis—Part 2. American Academy of Neurology 2013; 2. http://www.audio-digest.org/adfwebcasts/pdfs/ca0214.pdf (accessed 21 March 2014). (LOE: 4)
  15. 15.0 15.1 15.2 15.3 15.4 15.5 15.6 15.7 15.8 15.9 Health Line. Multiple Sclerosis From Top to Bottom.http://www.healthline.com/health/multiple-sclerosis/effects-on-the-body. (Accessed: 23 March 2014)
  16. 16.00 16.01 16.02 16.03 16.04 16.05 16.06 16.07 16.08 16.09 16.10 16.11 16.12 16.13 National Institute of Neurological Disorders and Stroke. Multiple Sclerosishttps://www.ninds.nih.gov/Disorders/All-Disorders/Multiple-Sclerosis-Information-Page#disorders-r1
  17. Sean Horton, Dany J. MacDonald, Karl Erickson; MS, exercise, and the potential for older adults.fckLREur Rev Aging Phys Act. 2010; 7:49–57 (LOE: 1A)
  18. Rietberg MB, Brooks D, Uitdehaag BM, Kwakkel G. Exercise therapy for multiple sclerosis. The Cochrane Library. 2004. Issue 3. (LOE: 1A)
  19. 19.0 19.1 Halabchi F, Alizadeh Z, Sahraian MA, Abolhasani M. Exercise prescription for patients with multiple sclerosis; potential benefits and practical recommendations.https://www.ncbi.nlm.nih.gov/pubmed/28915856 BMC neurology. 2017 Dec;17(1):185.
  20. 20.0 20.1 20.2 Provance, P. Physical Therapy in Multiple Sclerosis Rehabilitation. New York: A Clinical Bulletin from the Professional Resource Center of the National Multiple Sclerosis Society, 2011. (LOE: 1C) http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Clinical-Bulletin-Physical-Therapy-in-Multiple-Sclerosis-Rehabilitation.pdf (accessed 23 March 2014)
  21. Langer-Gould A, Lucas R, Xiang AH, Chen LH, Wu J, Gonzalez E, Haraszti S, Smith JB, Quach H, Barcellos LF.[1] MS Sunshine Study: Sun Exposure But Not Vitamin D Is Associated with Multiple Sclerosis Risk in Blacks and Hispanics. Nutrients. 2018 Feb 27;10(3):268.
  22. European-wide recommendations on rehabilitation for people affected by multiple sclerosis; EMSP and R.I.MS; October 2004(LOE: 1C)
  23. Döring A, Pfueller CF, Paul F, Dörr J. Exercise in multiple sclerosis--an integral component of disease management.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375103/ EPMA Journal. 2012 Dec 1;3(1):2.
  24. 24.0 24.1 Döring et al. Exercise in multiple sclerosis – an integral component of disease management. EPMA Journal. 2012 Dec 1;3(1):2. (LOE: 1A)
  25. Halabchi F, Alizadeh Z, Sahraian MA, Abolhasani M. Exercise prescription for patients with multiple sclerosis; potential benefits and practical recommendations. BMC neurology. 2017 Dec;17(1):185.
  26. Cameron MH, Lord S. Postural control in multiple sclerosis: implications for fall prevention.https://www.ncbi.nlm.nih.gov/pubmed/20567946/ Current neurology and neuroscience reports. 2010 Sep 1;10(5):407-12.
  27. Kasser SL, Jacobs JV, Ford M, Tourville TW. Effects of balance-specific exercises on balance, physical activity and quality of life in adults with multiple sclerosis: a pilot investigation.https://www.ncbi.nlm.nih.gov/pubmed/25738911 Disability and rehabilitation. 2015 Nov 20;37(24):2238-49.
  28. Seebacher B, Kuisma R, Glynn A, Berger T. The effect of rhythmic-cued motor imagery on walking, fatigue and quality of life in people with multiple sclerosis:https://www.ncbi.nlm.nih.gov/pubmed/27055804 A randomised controlled trial. Multiple Sclerosis Journal. 2017 Feb;23(2):286-96.
  29. Seebacher B, Kuisma R, Glynn A, Berger T. Exploring cued and non-cued motor imagery interventions in people with multiple sclerosis:https://www.ncbi.nlm.nih.gov/pubmed/29507773 a randomised feasibility trial and reliability study. Archives of physiotherapy. 2018 Dec;8(1):6.
  30. C. Bronson, K. Brewerton, J. Ong.; Does hippotherapy improve balance in persons with multiple sclerosis: a systematic review.; Eur J Phys Rehabil Med. 2010 ; 46(3):347–53(LOE:1A)
  31. Stergiou A, Tzoufi M, Ntzani E, Varvarousis D, Beris A, Ploumis A. Therapeutic Effects of Horseback Riding Interventions: https://www.ncbi.nlm.nih.gov/pubmed/28252520A Systematic Review and Meta-analysis. American journal of physical medicine & rehabilitation. 2017 Oct 1;96(10):717-25.
  32. Muñoz-Lasa S, Ferriero G, Valero R, Gomez-Muñiz F, Rabini A, Varela E.https://www.ncbi.nlm.nih.gov/pubmed/22452106 Effect of therapeutic horseback riding on balance and gait of people with multiple sclerosis. G Ital Med Lav Ergon. 2011 Oct;33(4):462-7.
  33. Koca TT, Ataseven H. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175116/What is hippotherapy? The indications and effectiveness of hippotherapy. Northern clinics of Istanbul. 2015;2(3):247.
  34. G. Roehrs, Gregory M. Karst; Effects of an Aquatics Exercise Program on Quality of Life Measures for Individuals with Progressive Multiple Sclerosis; Journal of Neurological Physical Therapy. 2004; 28, 63-71(LOE:1C)
  35. Van den Akker LE et al. Effectiveness of cognitive behavioral therapy for the treatment of fatigue in patients with multiple sclerosis: A systematic review and meta-analysis. J Psychosom Res. 2016;90:33-42 (LOE: 1A)
  36. Nazarboland N et al. Effectiveness of Cognitive Behavioral Therapy for Multiple Sclerosis (MS) Fatigue. Int J Behav Sci. 2017; 11(1): 19-24 (LOE: 2B)
  37. Hind et al. Cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: a systematic review and meta-analysis. BMC Psychiatry. 2014;14:5 (LOE: 1A)
  38. https://www.amymyersmd.com/2018/02/7-foods-fight-inflammation/
  39. 39.0 39.1 39.2 https://www.nationalmssociety.org/NationalMSSociety/media/Mid-America/Stay%20Informed/MS-Connection-Summer16.pdf
  40. https://www.amymyersmd.com/2018/01/2-foods-never-eat/
  41. https://multiplesclerosisnewstoday.com/2017/09/15/ms-patients-who-take-probiotics-ma-improve-certain-disease-parameters-study-suggests/
  42. Kouchaki E, Tamtaji OR, Salami M, Bahmani F, Kakhaki RD, Akbari E, Tajabadi-Ebrahimi M, Jafari P, Asemi Z. https://www.ncbi.nlm.nih.gov/pubmed/27669638Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Clinical Nutrition. 2017 Oct 1;36(5):1245-9.
  43. Brown SJ. The role of vitamin D in multiple sclerosis. Annals of Pharmacotherapy.https://www.ncbi.nlm.nih.gov/pubmed/16684809 2006 Jun;40(6):1158-61.
  44. https://www.nationalmssociety.org/Research/Research-News-Progress/Vitamin-D
  45. Nordvik I, Myhr KM, Nyland H, Bjerve KS. Effect of dietary advice and n‐3 supplementation in newly diagnosed MS patientshttps://www.ncbi.nlm.nih.gov/pubmed/10987373. Acta Neurologica Scandinavica. 2000 Sep 1;102(3):143-9.
  46. https://www.nationalmssociety.org/About-the-Society/News/Dietary-Omega-3-Fatty-Acids-Linked-to-Lower-Risk-o
  47. https://www.nationalmssociety.org/Living-Well-With-MS/Diet-Exercise-Healthy-Behaviors/Diet-Nutrition/Omega-3
  48. Carvalho KS. Mitochondrial dysfunction in demyelinating diseases.https://www.ncbi.nlm.nih.gov/pubmed/24331361 InSeminars in pediatric neurology 2013 Sep 1 (Vol. 20, No. 3, pp. 194-201). Elsevier.
  49. Witte ME, Mahad DJ, Lassmann H, van Horssen J. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis.https://www.ncbi.nlm.nih.gov/pubmed/24369898 Trends in molecular medicine. 2014 Mar 1;20(3):179-87.
  50. Storoni M, Plant GT. The therapeutic potential of the ketogenic diet in treating progressive multiple sclerosis.Storoni M, Plant GT. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709725/ Multiple sclerosis international. 2015;2015.