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Multiple Sclerosis

MS

Multiple sclerosis (MS, disseminated sclerosis, encephalomyelitis disseminata) is an inflammatory demyelinating disease of the central nervous system. Multiple sclerosis is divided into the following categories: Relapsing-remitting MS, Secondary progressive MS, Primary progressive MS and Progressive-relapsing MS.


Presentation

Individuals with multiple sclerosis can present almost any form of neurological symptom [7]. The most common problems are sensory, autonomic, visual and motor. The specific symptoms are determined by where the lesions are located within the nervous system. General presentations include the following:

  • Loss of sensitivity or changes in response to sensations
  • Very pronounced reflexes
  • Muscle weakness
  • Numbness
  • Problems with swallowing or speech
  • Difficulties in coordination and balance
  • Visual problems 
  • Acute or chronic pain
  • Excessive tiredness
  • Difficulties with bladder and bowel movements
  • Thinking difficulties
  • Depression and mood swings
Fatigue
  • Physical behaviour is weakly associated with physical fatigue and is not associated with other dimensions of fatigue.[ncbi.nlm.nih.gov]
  • Sleep disorders and fatigue are common in multiple sclerosis (MS). The underlying causes are not fully understood, and prospective studies are lacking.[ncbi.nlm.nih.gov]
  • Also, screening and treatment of fatigue as the most important predictor for HRQOL is necessary.[ncbi.nlm.nih.gov]
  • In terms of HRQoL, natalizumab seems to benefit mostly patients with more marked fatigue at baseline.[ncbi.nlm.nih.gov]
  • Insufficiently active PwMS demonstrated a slower walking speed, elevated fatigue, more concerns of falling and additional walking difficulties compared to active PwMS.[ncbi.nlm.nih.gov]
Weakness
  • After improvement in motor weakness, we found that the lower amplitude of the readiness field and decreased ECD strength of the MEF observed in affected hemisphere during motor weakness had recovered.[ncbi.nlm.nih.gov]
  • She was currently in a remission phase from her MS but with persistent sequelae, including impaired eyesight and muscle weakness of the limbs.[ncbi.nlm.nih.gov]
  • Despite aggressive treatment, he developed significant weakness in ankle dorsiflexors and hip and knee flexors and was no longer capable of consistently taking a step on his own.[ncbi.nlm.nih.gov]
  • A 33-year-old man with gait instability, weakness of the left lower extremity, decreased visual acuity in the left eye, and urgency and urine incontinence was diagnosed of relapsing-remitting multiple sclerosis.[ncbi.nlm.nih.gov]
  • The following case is a patient with unilateral weakness and radiologic findings that were concerning for a high-grade glioma. Peripheral studies were equivocal.[ncbi.nlm.nih.gov]
Pain
  • Stride length and velocity are associated with the level of fatigue and pain, as well as the time of day.[ncbi.nlm.nih.gov]
  • Subjectively, patient also reported pain relief, mobility and fatigue improvement.[ncbi.nlm.nih.gov]
  • One week after the third cycle of rituximab (6 doses of 1000 mg), she experienced abdominal pain, fever, and severe bloody diarrhea; finally, she was diagnosed with ulcerative colitis (UC).[ncbi.nlm.nih.gov]
  • Investigators at the University of California at San Diego report that inhaled cannabis significantly reduces objective measures of pain intensity compared to placebo in patients with MS.[norml.org]
  • Approximately 70% of the patients complained at least 1 SD (decreased libido, erectile dysfunction, premature or retarded ejaculation, painful penetration), and 22% of them reported the disorder as frequent.[ncbi.nlm.nih.gov]
Falling
  • Outcome measures included the Godin Leisure-Time Exercise Questionnaire (GLTEQ), Four Square Step Test (FSST), 2-Minute Walk test (2 mWT), Timed Up and Go test (TUG), Timed 25-Foot Walk test (T25FW), fall status, Falls Efficacy Scale International (FES-I[ncbi.nlm.nih.gov]
  • […] pathophysiology believed to be caused by a combination of genetic, environmental and infectious factors recent research suggests a T-cell mediated autoimmune mechanism Associated conditions orthopaedic increased fracture risk relating to increased risk of falling[orthobullets.com]
  • Learning from the Life and Loss of Stan Lee Columns , Fall Down, Get Up Again- a Column by John Connor And the Good News Is … Columns , The MS Wire - A Column by Ed Tobias When You’ve Gotta Go, but There’s No Place to Do It News Celgene and Lyfebulb Partner[multiplesclerosisnewstoday.com]
  • In that case, however, people with M.S. should also have a high incidence of broken bones because of their falls.[nytimes.com]
  • Difficulty walking can lead to injuries due to falling.[healthline.com]
Difficulty Walking
  • As the disease progresses, symptoms may advance to include muscle spasms, heat sensitivity, vision problems, depression, difficulty speaking or swallowing, tremors, dizziness, impaired thinking or perception and difficulty walking (gait disorders).[uwmedicine.org]
  • Difficulty walking can lead to injuries due to falling.[healthline.com]
  • Symptoms, like fatigue, difficulty walking, vision problems and cognitive changes, can be severe and disabling, and can take a heavy toll on patients.[cbsnews.com]
  • However, common symptoms of MS include changes in sensation or sensory symptoms such as tingling and numbness, and changes in muscle function or motor symptoms such as difficulty walking, stiffness or tremors.[ucsfhealth.org]
  • That leads to problems like: vision problems fatigue or weakness difficulty walking or trouble with balance or coordination numbness or the pins-and-needles tingling you feel when your foot falls asleep memory problems MS is mostly a disease that adults[kidshealth.org]
Fecal Incontinence
  • incontinence,increased gut permeability and increased occurrence of inflammatory bowel diseases in MS patients and their families,suggest an important gut–CNS connection.[physio-pedia.com]
Diplopia
  • The patient presented with progressive decrease of visual acuity, intermittent diplopia, paresthesia of the left arm and equilibrium disturbances.[ncbi.nlm.nih.gov]
  • […] episodes of neurological dysfunction (brain, spinal cord or optic nerves) that are separated in time and space Symptoms symptoms of disease are based on the systems involved psych fatigue, depression, mood disorders central nervous system optic neuritis , diplopia[orthobullets.com]
  • Eye problems : In addition to the optic neuritis that comes with CIS, MS can cause: Nystagmus : involuntary eye movements Diplopia: double vision Fatigue : You may feel very tired .[webmd.com]
  • […] sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, or diplopia[disabled-world.com]
  • Examples of common clinical features include 23,24 : brainstem and cranial nerve involvement: optic neuritis internuclear ophthalmoplegia (often bilateral) trigeminal neuralgia diplopia (e.g. due to abducens nerve palsy ) vertigo cerebellum involvement[radiopaedia.org]
Blurred Vision
  • Female aged 16, with Relapsing Remitting Multiple sclerosis (RRMS) was reported with initial symptoms of blurred vision, severe immobility, upper and lower limb numbness and backache.[ncbi.nlm.nih.gov]
  • Common early symptoms may include fatigue, numbness, tingling, muscle weakness, blurred vision or loss of balance.[uwmedicine.org]
  • Symptoms Some examples of the symptoms seen in MS include: Vision problems such as blurred vision, double vision or paralysis of eye muscles Muscle stiffness and lack of balance and co-ordination. There is loss of dexterity and fine movement.[news-medical.net]
  • Common symptoms of a relapse may include: Fatigue Numbness Tingling Blurred vision, double vision or loss of vision Unsteady gait Weakness These symptoms tend to persist for days or weeks, and then disappear partially or completely on their own or with[hopkinsmedicine.org]
  • Not every MS patient will experience the disease in the same way, but the most common early symptoms are: Blurred vision or double vision Clumsiness or coordination problems Loss of balance Numbness, tingling, itching or burning sensations Thinking problems[loyolamedicine.org]
Eye Pain
  • Early MS symptoms may include: weakness/fatigue loss of balance problems with coordination tremors tingling and/or numbness blurred or loss of vision muscle stiffness/cramping thinking problems depression bowels problems facial or eye pain It is still[drfuhrman.com]
  • You may also have some eye pain. It isn’t uncommon for these early symptoms to go away only to return later. You may go weeks, months, or even years between flare-ups. These symptoms can have many different causes.[healthline.com]
  • Common symptoms include: Vision problems, including double vision, blurriness, partial color blindness, eye pain, partial or complete loss of vision in one eye Thinking and memory problems Fatigue Muscle weakness, dizziness or tremor Numbness or weakness[familydoctor.org]
  • Call your doctor if you have changes in vision, redness, or eye pain. Liver damage. Symptoms of liver damage include yellowing of the skin and eyes (jaundice), unusual darkening of the urine, nausea, feeling tired or weak, or vomiting.[avonex.com]
  • Most patients (n 13, 68 %) presented with blurred vision, decreased VA, or eye pain. Macular edema was diagnosed within 3 to 4 months of treatment initiation in most cases (n 13, 68 %); 2 patients had late onset (greater than 12 months) ME.[aetna.com]
Restless Legs Syndrome
  • Secondary objectives were to investigate correlations of sleep quality and daytime sleepiness (ESS), depression (HADS-D), anxiety (HADS-A), pain (HSAL), and restless legs syndrome (RLS).[ncbi.nlm.nih.gov]
Facial Pain
  • Symptoms and signs of MS are extremely variable and range from mild to severe, and may include: Problems with balance when walking Hearing loss Facial pain Weakness Muscle spasms that cause pain.[emedicinehealth.com]
  • 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[physio-pedia.com]
Emotional Lability
  • Vertigo, incoordination and other cerebellar problems, depression, emotional lability, abnormalities in gait, dysarthria, fatigue and pain are also commonly seen.[library.med.utah.edu]
Dizziness
  • When the myelin is damaged, the nerve impulses are not transmitted as quickly or efficiently, resulting in symptoms such as numbness in the limbs, fatigue, dizziness, paralysis and/or loss of vision.[benaroyaresearch.org]
  • As the disease progresses, symptoms may advance to include muscle spasms, heat sensitivity, vision problems, depression, difficulty speaking or swallowing, tremors, dizziness, impaired thinking or perception and difficulty walking (gait disorders).[uwmedicine.org]
  • However we know that common symptoms of MS include numbness or tingling in various parts of the body, weakness of one or more parts of the body, walking difficulties, dizziness, fatigue, visual blurring, and occasionally double vision.[my.clevelandclinic.org]
  • Prolonged double vision Tingling or pain in parts of your body Electric-shock sensations that occur with certain neck movements, especially bending the neck forward (Lhermitte sign) Tremor, lack of coordination or unsteady gait Slurred speech Fatigue Dizziness[mayoclinic.org]
  • […] symptoms are: Blurred vision or double vision Clumsiness or coordination problems Loss of balance Numbness, tingling, itching or burning sensations Thinking problems Weakness in an arm or leg Later symptoms include: Bowel problems Cognitive problems Dizziness[loyolamedicine.org]
Tremor
  • As the disease progresses, symptoms may advance to include muscle spasms, heat sensitivity, vision problems, depression, difficulty speaking or swallowing, tremors, dizziness, impaired thinking or perception and difficulty walking (gait disorders).[uwmedicine.org]
  • However, common symptoms of MS include changes in sensation or sensory symptoms such as tingling and numbness, and changes in muscle function or motor symptoms such as difficulty walking, stiffness or tremors.[ucsfhealth.org]
  • , usually in one eye at a time, often with pain during eye movement Prolonged double vision Tingling or pain in parts of your body Electric-shock sensations that occur with certain neck movements, especially bending the neck forward (Lhermitte sign) Tremor[mayoclinic.org]
  • […] coordination problems Loss of balance Numbness, tingling, itching or burning sensations Thinking problems Weakness in an arm or leg Later symptoms include: Bowel problems Cognitive problems Dizziness Fatigue Muscle spasms Sexual problems Speech problems Tremors[loyolamedicine.org]
  • Some people experience muscle weakness, poor balance, poor coordination, muscle tightness or spasticity, tremors or paralysis, which may be temporary or permanent.[slhn.org]
Stroke
  • We narrate the case of a 28-year gentleman known to have severe mitral stenosis, who presented with history of multiple stroke-like episodes. During each episode, he had CT brain done and was labelled as having recurrent embolic strokes.[ncbi.nlm.nih.gov]
  • She has recurrent posterior circulation stroke-like symptoms, hearing loss and acroparaesthesia, but typical radiological features of MS on MRI brain. Later she developed an ischaemic stroke, infiltrative cardiomyopathy and chronic renal failure.[ncbi.nlm.nih.gov]
  • Comparisons were made of yawners and non-yawners, healthy volunteers and MS participants. chronic fatigue, diabetes, fibromyalgia, heart condition, high blood pressure, hormone replacement therapy, stroke.[ncbi.nlm.nih.gov]
  • Recently, transcranial direct current stimulation (tDCS) has been proven to be effective in ameliorating swallowing problems in stroke patients.[ncbi.nlm.nih.gov]
  • A 34-year old Caucasian female was initially diagnosed with multiple small-vessel strokes at age 20 years which were etiologically classified as secondary to anti-phospholipid antibody syndrome (APS) although she had no history or laboratory data to suggest[ncbi.nlm.nih.gov]
Ataxia
  • An 80-year-old man developed dysarthria, quadriplegia, sensory disturbance and ataxia in all limbs. Brain and spinal magnetic resonance imaging (MRI) revealed multiple enhanced lesions.[ncbi.nlm.nih.gov]
  • We report the case of a 50-year-old man who presented with progressive gait ataxia. Brain magnetic resonance imaging (MRI) on fluid-attenuated inversion recovery revealed a hyperintense lesion in the right temporal white matter.[ncbi.nlm.nih.gov]
  • MS symptoms may include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction.[patientslikeme.com]
  • […] parasthesis, hypoesthesia, peculiar sensory phenomena's (e.g. sensation of wetness) GI incontinence, diarrhea, constipation urology incontinence, frequency, retention Physical exam inspection assess for gait abnormalities (e.g. wide-based gait, limb ataxia[orthobullets.com]
  • Early symptoms may include numbness and/or paresthesia, mono- or paraparesis, double vision, optic neuritis, ataxia, and bladder control problems.[library.med.utah.edu]
Dysarthria
  • In MS patients, maximum expiratory times, maximum phonation times, and dysarthria scores were significantly altered compared to healthy controls.[ncbi.nlm.nih.gov]
  • An 80-year-old man developed dysarthria, quadriplegia, sensory disturbance and ataxia in all limbs. Brain and spinal magnetic resonance imaging (MRI) revealed multiple enhanced lesions.[ncbi.nlm.nih.gov]
  • MS symptoms may include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction.[patientslikeme.com]
  • Vertigo, incoordination and other cerebellar problems, depression, emotional lability, abnormalities in gait, dysarthria, fatigue and pain are also commonly seen.[library.med.utah.edu]
  • Typical symptoms include paresthesia, weakness, ataxia, dysarthria, sensory deficits, and impaired or double vision. Fatigue and psychiatric symptoms, such as depression or euphoria, can also be manifestations of MS.[clinicaladvisor.com]
Urinary Incontinence
  • If nerve fibers to the bladder are affected, urinary incontinence may occur. Likewise, damage to the cerebellum portion of the brain may result in imbalance or a lack of coordination.[ucsfhealth.org]
  • incontinence others: fatigue depression Uhthoff phenomenon: heat and exercise worsen symptoms cognitive decline Classification A number of patterns of longitudinal disease have been described 11,12 : relapsing-remitting most common (70% of cases) patients[radiopaedia.org]
  • 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[physio-pedia.com]
  • FDA approves Botox to treat specific form of urinary incontinence. August 25, 2011. Available at . Accessed: November 28, 2011. Beck RW, Cleary PA, Anderson MM Jr, et al.[emedicine.medscape.com]
Sexual Dysfunction
  • Studies on the prevalence of sexual dysfunction (SD) in multiple sclerosis (MS) have shown that 40% to 80% of women and 50% to 90% of men have had sexual complaints.[ncbi.nlm.nih.gov]
  • dysfunction Sildenafil and other agents for men† Maximize DMT Identify and address contributing MS symptoms (i.e., bladder and fatigue) Streamline/minimize medication with untoward side effects on sexual dysfunction (i.e., SSRIs) Appropriate referral[clevelandclinicmeded.com]
  • dysfunction: Oral phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil, vardenafil) Optic neuritis: Intravenous methylprednisolone may speed recovery See Treatment and Medication for more detail.[emedicine.medscape.com]
Urinary Retention
  • retention A constant state of tiredness or fatigue There appears to be a relationship between multiple sclerosis, higher temperatures, and the worsening of symptoms.[emedicinehealth.com]
  • retention ) Muscle spasticity Incoordination of muscles Tremor Painful involuntary muscle contractions Slurred speech Fatigue There are four types of MS: Relapsing-remitting multiple sclerosis (RRMS), Secondary-progressive multiple sclerosis (SPMS),[medicinenet.com]

Workup

Many patients seek medical help following an initial attack of symptoms often referred to as a clinically isolated syndrome or CIS. Some people who have a CIS do not go on to develop full multiple sclerosis and it is difficult to predict which patient will develop it and which one wouldn’t [8].

Since there is no definitive test for it, diagnosing multiple sclerosis is often a challenge. This is because there are many conditions that present the same symptoms as MS. For a confirmed diagnosis of multiple sclerosis, the doctor must find the following:

  • Evidence of nerve damage in at least two different areas of the central nervous system (brain, spinal cord, and optic nerves)
  • Evidence that the damage occurred in episodes that happened at least one month apart
  • No evidence that the damage is caused by other conditions
HLA-DR2
  • […] swollen subacute stage plaques become paler in colour ("chalky") abundant macrophages chronic stage (inactive plaques/gliosis) little or no myelin breakdown gliosis with associated volume loss appear grey/translucent Associations a strong association with HLA-DR2[radiopaedia.org]

Treatment

Presently there is no cure for MS but symptoms of MS can often be eased with the right medications [9].

Treatments generally fall into four categories:

  • Medicines that aim to modify the disease process.
  • Steroid medication to treat relapses.
  • Other medicines to help ease symptoms.
  • Other therapies and general support to minimise disability.

Prognosis

Except on rare occasions when the disease is severe, multiple sclerosis isn’t fatal. Many people with multiple sclerosis go on live to the average life expectancy for their sex in their region of residence. Most of them die of natural causes that affect everyone else [6]. However, the symptoms of MS can negatively affect the quality of life. This is perhaps why the rate of suicide amongst patients with multiple sclerosis is higher than normal.

Most patients with multiple sclerosis do not become severely disabled. Generally, most people diagnosed of the condition remain ambulatory without need for a wheelchair 20 years from time of initial diagnosis. However, many may have to use some sort of walking aid.

Etiology

As is the cases with most autoimmune conditions, the exact cause of MS is unknown. However, it is believed that a combination of environmental and genetic factors play different roles.

Although multiple sclerosis isn’t hereditary, it appears that genetic factors help in making certain individuals susceptible to the disease process that leads to this condition. The major histocompatibility complex (MHC) is where the most significant genetic link to MS occurs. The MHC is a cluster of genes found on the Chromosome 6 that are important for the functions of the immune system.

Also, multiple sclerosis is most common in specific geographical regions in the world especially areas that are most far off from the equator (northern Europe and northern American countries). With the cluster of Multiple Sclerosis in this region, researchers have continued to investigate the role played by toxins, infections, deficiency in certain vitamins like the Vitamin D may be playing a major role in triggering MS in individuals that are susceptible genetically [3].

Epidemiology

The number of individuals with multiple sclerosis around the world has been put at 2.5million approximately meaning that 30 out of every 100,000 people develop the condition. However, the rates vary greatly in based on regions [4]. It has been estimated that 18,000 deaths are recorded each year as a result of this condition. In America, incidence is 8.3 per 1000,000, in Europe 80 per 100,000. In South East Asia incidence is 2.8 per 100,000 people while in Africa rates are less than 0.5 cases per 100,000.

Rates of multiple sclerosis may appear to be increasing but this can be put down to better diagnosis available across board today.

The disease is seen mostly in adults in their late twenties or early thirties and rarely in childhood or after 50 years of age. Primary progressive multiple sclerosis is mostly seen in people in their late 50s. Also, as is the case with most autoimmune disorders, the disease is more common in women and the trend has continued to increase. In rare cases where children are affected, more females than males are affected.

Sex distribution
Age distribution

Pathophysiology

The three major characteristics of MS are the formation of lesions or plaques in the central nervous system, destruction of the myelin sheath of neurons and inflammation [5]. These interact in a complex manner that is not yet understood till date to initiate the disintegration of the nerve tissue and in turn, bring about the signs and symptoms of the disease. Damage is believed to be caused at least in part by attack on the nervous system by the individual's immune system.

Prevention

There is no way to prevent multiple sclerosis and its attacks.

Summary

Also known as disseminated sclerosis or encephalomyelitis disseminata, multiple sclerosis (MS) is an inflammatory disease that damages the insulating covers of the nerve cells in the brain and the spinal cord [1]. This damage disrupts the ability of parts of the nervous system to communicate with the body and this brings about a wide range of symptoms which may cause psychiatric, mental or physical problems for the affected individual.

Multiple sclerosis takes several forms with each new symptom building up over a period of time (progressive forms) or occurring in relapsing forms (isolated attacks). Between the various attacks, some of the symptoms of MS disappears but it is possible to see permanent neurological problems as the disease continues to progress [2].

Patient Information

Multiple sclerosis is a disease that turns your immune system against the protective sheath covering your nerves (known as the myelin sheath).

When this happens, the communication between your brain and other parts of your body is affected. At the end of the day the nerves affected may deteriorate. This process is not reversible yet. 

The signs and symptoms of this condition varies widely as it is dependent on the amount of damage done to the nerves and what particular nerves were affected. In severe cases, people with this condition lose their ability to walk independently and in some instances, the individual may not see development of any new symptoms. 

Currently, there is no cure for multiple sclerosis but with treatments, the patient can recover properly from attacks and the symptoms of the condition can be managed. The treatments can also help in modifying the course of the disease.

References

Article

  1. Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. Dec 2005;58(6):840-6. 
  2. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. Mar 1983;13(3):227-31. 
  3. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. Apr 1996;46(4):907-11.
  4. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. Jul 2001;50(1):121-7. 
  5. Sanford M, Lyseng-Williamson KA. Subcutaneous recombinant interferon-ß-1a (Rebif®): a review of its use in the treatment of relapsing multiple sclerosis. Drugs. Oct 1 2011;71(14):1865-91
  6. Calabresi P. Multiple sclerosis and demyelinating conditions of the central nervous system. In: Goldman L, Ausiello D, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2012:chap 419.
  7. Farinotti M, Simi S, Di Pietrantonj C, McDowell N, Brait L, Lupo D, Filippini G. Dietary interventions for multiple sclerosis. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004192.
  8. Kappos L, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, et al. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet. 2007 Aug 4;370(9585):389-97.
  9. Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):416-26. Epub 2010 Jan 20.
  10. Khan F, Ng L, Turner-Stokes L. Effectiveness of vocational rehabilitation intervention on the return to work and employment of persons with multiple sclerosis. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD007256002819.

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Last updated: 2018-06-22 06:05