MS Multiple Sclerosis
- 1 Definition/Description
- 2 Prevalence
- 3 Characteristics/Clinical Presentation
- 4 Associated Co-morbidities
- 5 Medications
- 6 Diagnostic Tests/Lab Tests/Lab Values
- 7 Etiology/Causes
- 8 Systemic Involvement
- 9 Medical Management (current best evidence)
- 10 Physical Therapy Management (current best evidence)
- 11 Differential Diagnosis
- 12 Case Reports/ Case Studies
- 13 Resources
- 14 Recent Related Research (from Pubmed)
- 15 References
Multiple sclerosis (MS) is a complex, chronic, neurological disease affecting the insulation (myelin) surrounding the nerve fibres (axons) of the central nervous system, particularly the brain, spinal cord and optic nerve. . MS is an autoimmune disorder characterized by inflammation, demyelination and gliosis Myelin protects nerve cells and allows the efficient transmission of electrical impulses along nerve fibres. MS is an autoimmune disorder characterized by inflammation, demyelination and gliosis. 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. 
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 describe 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. 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.
It is estimated that in the United States there are 400,000 people being affected by MS and 2.1 million people globally. Females are 2 to 3 times more likely to have MS than males, which may indicate hormones play a role in acquiring the disease. The prevalence of MS has increased within the last 5 decades with the increase primarily being due to females. 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. 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%. MS can occur in many ethnics groups, with the most common populations being Caucasians with an ancestry from nothorn Europe, followed by African-Americans, latinos/hispanics and asians. It is rarely seen in ethnic populations such as, Australian Aborigines, New-Zealanders, Yakutes, Inuit, Hungarian Romani and Norwegian Lapps. 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.
Multiple Sclerosis will present with varying symptoms because it depends on the location of the nerves being affected. 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 develope. 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. Other common symptoms presented with MS are:
- 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. An increase in symptoms can occur with an increase in body temperature because many MS patients have a sensitivity to heat. 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.  It afflicts women more often than men (ratio of approximately 2:1). 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.
• Inflammatory bowel disease
• Thyroid disease
• Systemic lupus erythematosus
• Heart disease
• Chronic lung disease
• Sleep disorders
• Alcohol use
Other less common comorbid conditions include: kidney disease, asthma, cancer, Sjogren’s syndrome, and liver disease .
Acute Relapse Managment: work as immunosuppressents and anti-inflammatory drugs to reduce CNS swelling.
• Prednisone: Oral corticosteriod used for inflammation relief during acute relapses. Often a high-dose of a corticosteriod is provided intravenously immediately following an exacerbation then an oral dose of prednisone is introduced as a supplement therapy. Side effects include sleep disturbance, headache, excessive sweating, or increased hair growth. Prolonged corticosteroid use can also lead to skin problems, edema of face or lower extremities, arthralgias, irregular menstration, muscle cramps, and pain.
o Brand Name: Deltasone
• Plasmapheresis: Plasma exchange to reduce potentially harmful antibodies from the body. 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.
Disease-Modifying Agents: work to slow progress or reduce the number of MS attacks
• Beta Interferons. Interferons work to reduce the number of attacks and lessen the severity of MS attacks during early stages of RRMS . Common side effects include reaction to injection site, liver damage, fever, chills, muscle pains, or fatigue. 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 .
o Brand Names: Avonex, Betaseron, Extavia, and Rebif
• Glatiramer acetate. Injectable disease-modifying drugs that may help alter immune cells from attacking myelin. The exact mechanism of action is not entirely understood. Mild side effects include injection site irritation or allergic reactions; more rare side effects include flushing, anxiety, chest pain, or heart palpitations.
o Brand Name: Copaxone
•Mitoxantrone. Injectable drug given four times per year that suppresses immune functions thought to attack myelin. This drug is approved for treating SPMS, PRMS, and RRMS. In a small percentage (~1%) this drug has been correlated with some types of blood cancers and can be harmful the heart. 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. 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 .
o Brand Name: Novantrone
• Natalizumab. This drug is given monthly by intravenous infusion and works by preventing possibly damaging immune cells from entering the brain or spinal cord. The drug is approved for treating relapsing forms of MS, especially in those that are not responding to other treatments. However, those taking Natalizumab are at an increased risk for developing progressive multifocal leukoencephalopathy (PML), a viral infection that can be fatal. Side effects include headache, fatigue, depression, diarrhea, abdominal pain, UTI and GI distress.
oBrand Name: Tysabri
• Fingolimod. A new drug that is the first MS daily oral treatment for those with RRMS. The disease-modifying agent works by preventing specific lymphocytes from exiting lymph nodes and entering the central nervous system (CNS). 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. Side effects include headach, influenza, diarrhea, back pain, abnormal liver tests, and cough.
oBrand Name: Gilenya
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.
Magnetic Resonance Imaging (MRI):
An MRI is a device in which powerful radio waves produce detailed images of the brain and spinal cord.An MRI is very sensitive in detecting MS plaques that are found in the white matter of the brain and spinal cord. 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.
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. The cerebral spinal fluid is tested for abnormal amount of white blood cells, proteins and other abnormalities that are secondary to MS.
Evoked Potential Test:
The evoked potential test measures electrical signals in the nerves sent from the brain in response to a stimuli. The stimulus may be visual or electrical in origin. 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.
A blood test is beneficial to perform to rule out other conditions that may present similar to MS, such as infectious or inflammatory diseases.
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 factors: The body's own immune cells attack the CNS and ultimately destroy nerve conduction. 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.
Environmental factors: 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.
Genetic factors: 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
Infectious factors: There is a possibility that viruses and other infectious agents may trigger the onset of MS. Many viral and bacterial infections are being investigated, however there is no definitive evidence that shows they may be the cause of MS.
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. MS impacts the brain with symptoms such as, memory loss, confusion, dizziness, vertigo, personality changes, depression and less commonly, seizures.
Vestibular System: Vision disturbances are a common first symptom with MS that come on suddenly in one or both eyes. Symptoms may present as blurred or double vision, pain, and trouble seeing contrast in one or both eyes. 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. Problems with hearing usually occur due to damage to the brainstem and most commonly resolve on their own.
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. 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.
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. 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.
Autonomic System: MS can affect the bladder when damage to the nerves that control bladder and sphincter function occurs. 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. 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. 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.
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.
Medical Management (current best evidence)
Currently there is no cure for MS. However, there are numerous medications available in assisting acute attacks, disease progression, and to help manage symptoms .
Typically, a high dose of a corticosteroid, such as methylprednisolone, is the first line of treatment against an attack of MS. Corticosteriods help to reduce and inflammation by suppressing the immune system, and when given intravenously can work quickly . Oral doses are often given as follow-up treatments during acute exacerbations . Side effects of corticosteroids may include: mood swings, seizures, weight gain, and can put the individual at an increased risk of infection due to immune system suppression . Long term use of corticosteriods can lead to hypertension, diabetes, aseptic femoral necrosis, osteopenia, and peptic ulcers. As a supplemental or secondary treatment, plasmapheresis (plasma exchange) can be used in relapsing forms of MS to help control MS attacks . 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 .
Additional medical treatment includes drug interventions to help reduce disease progression . Disease-modifying agents are most commonly used for decreasing relapses in patients with RRMS . 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 . The following disease-modifying drugs work to slow progress or reduce the number of MS attacks.
Symptom management 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.
Medical management for:
• Spasticity is best treated on an individual basis. The most common treatments include muscle relaxants such as baclofen or tizanidine (Zanaflex). Other medications include diazepam (Valium), dantrolene (Dantrium), phenol, or botulinum toxin (Botox).
• Pain is a common symptom present in MS and can present acutely or as chronic pain .
o Acute Pain Treatment
- Trigeminal neuralgia—stab-like facial pain with anticonvulsants
• Carbamazepine (Tegretol) or phenytoin (Dilantin)
- Lhermitte’s sign—stabbing, electric-shock pain along the back that is elicited with neck flexion treated with anticonvulsants
- Dysesthesias—burning, aching neurological pain can be treated with anticonvulsant or antidepressant medications
• Amitriptyline (Elavil), imipramine (Tofranil), gabapentin (Neurontin), desipramine (Norpramin)
- Paroxysmal Pain—sudden sharp pains that will respond to:
• Carbamazepine (Tegretol), amitriptyline (Elavil), phenytoin (Dilantin), diazepam (Valium), or gabapentin (Neurontin)
o Chronic Pain Treatment
- Burning, aching, “Pins & Needles—treated the similar to acute dysesthesias
• Gabapentin (Neurontin), amitriptyline (Elavil)
- Spasticity—muscle spasm medications range from over-the-counter to prescription anti-inflammatory drugs
• acetaminophen, ibuprofen, baclofen (Lioresal), tizanidine (Zanaflex)
• 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.
o Medical Management includes amantadine hydrochloride (Symmetrel), modafinil (Provigil)
• Tremor can present in varying degrees in different forms (intention, postural, resting, nystamgus) consequently, treatment response is also variable.
o Medical management includes hydroxyzine (Atarax, Vistaril), clonazepam (Klonopin), propranolol (Inderal), buspirone (Buspar), ondansetron (Zofran), primidone (Myosline), or meclizine (Antivert)
• 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.
o Memory deficit management has used donepezil (Aricept), a drug often used for the treatment of Alzheimer’s disease.
• Bowel & Bladder Impairments differ according to whether the issue is with storing to expelling contents.
o Bladder storage dysfunction (overactive, spastic bladder) is treated with anticholinergics (propantheline (Pro-Banthine), oxybutynin (Ditropan), imipramine (Tofranil).
o Bladder emptying dysfunction (flaccid bladder) is treated with alternative emptying techniques such as the Crede maneuver or intermittent self-catheterization.
o Dyssynergic bladder (combined dysfunction) is treated with alpha-adrenergic blocking like agents terazosin (Hytrin), prazosin (Minipress), tamsulosin (Flomax) and antispasticity agents such as baclofen.
o Constipation is treated through diet and bulk-forming supplements such as Metamucil, FiberCon, Citrucel, Benefiber or stool softeners.
For more information and drug listings on symptom management, please visit the following link:
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. 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. Analysing 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.
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.
Due to the progressive nature of the disease, those in the moderate stage might begin to notice impairments at varying degrees and activities of daily living (ADL) may require assistance. At this middle stage, PTs 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. 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. 
Another study was found that Hippotherapy has a positive effect on balance of persons with multiple sclerosis and has an added benefit of enhancing quality of life.  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.  Also aquatic exercise programs 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. 
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. Throughout all stages of MS a PT can offer psychological support to the patient and family/caregiver support and act as a referral so to adjunct healthcare professionals.
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.
- 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.
- 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.
- 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.
- 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.
- 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.
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:
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
Case Reports/ Case Studies
Recent Related Research (from Pubmed)
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- Mayo Clinic. Disease and Conditions Multiple Sclerosis. http://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/basics/symptoms/con-20026689.(Accessed: 21 March 2014)
- European-wide recommendations on rehabilitation for people affected by multiple sclerosis; EMSP and R.I.MS; October 2004(level D)
- Sean Horton, Dany J. MacDonald, Karl Erickson; MS, exercise, and the potential for older adults.fckLREur Rev Aging Phys Act. 2010; 7:49–57 (level A1)
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- European-wide recommendations on rehabilitation for people affected by multiple sclerosis; EMSP and R.I.MS; October 2004(level D)
- 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(level A1)
- Sean Horton, Dany J. MacDonald, Karl Erickson; MS, exercise, and the potential for older adults.fckLREur Rev Aging Phys Act. 2010; 7:49–57 (level A1)
- 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(level C)