- Author: Christopher Luzzio, MD; Chief Editor: Jasvinder Chawla, MD, MBA more...
Multiple sclerosis (MS) is an immune-mediated inflammatory disease that attacks myelinated axons in the central nervous system, destroying the myelin and the axon in variable degrees and producing significant physical disability within 20-25 years in more than 30% of patients. The hallmark of MS is symptomatic episodes that occur months or years apart and affect different anatomic locations. See the image below.
See Multiple Sclerosis, a Critical Images slideshow, for more information on incidence, presentation, and intervention, as well as additional resources.
Also, see the Autoimmune Disorders: Making Sense of Nonspecific Symptoms slideshow to help identify several diseases that can cause a variety of nonspecific symptoms.
Signs and symptoms
Classic MS signs and symptoms are as follows:
Sensory loss (ie, paresthesias): Usually an early complaint
Spinal cord symptoms (motor): Muscle cramping secondary to spasticity
Spinal cord symptoms (autonomic): Bladder, bowel, and sexual dysfunction
Cerebellar symptoms: Charcot triad of dysarthria, ataxia, and tremor
Trigeminal neuralgia: Bilateral facial weakness or trigeminal neuralgia
Facial myokymia (irregular twitching of the facial muscles): May also be a presenting symptom
Eye symptoms: Including diplopia on lateral gaze (33% of patients)
Constitutional symptoms: Especially fatigue (70% of cases) and dizziness
Pain: Occurs in 30-50% of patients at some point in their illness
Subjective cognitive difficulties: With regard to attention span, concentration, memory, and judgment
Depression: A common symptom
Euphoria: Less common than depression
Bipolar disorder or frank dementia: May be a late finding but is sometimes found at initial diagnosis
Symptoms associated with partial acute transverse myelitis
See Clinical Presentation for more detail.
MS is diagnosed on the basis of clinical findings and supporting evidence from ancillary tests. Tests include the following:
Magnetic resonance imaging: The imaging procedure of choice for confirming MS and monitoring disease progression in the CNS
Evoked potentials: Used to identify subclinical lesions; results are not specific for MS
Lumbar puncture: May be useful if MRI is unavailable or MRI findings are nondiagnostic; CSF is evaluated for oligoclonal bands and intrathecal immunoglobulin G (IgG) production
MS is divided into the following categories, principally on the basis of clinical criteria, including the frequency of clinical relapses, time to disease progression, and lesion development on MRI[1, 2, 3, 4] :
Relapsing-remitting MS (RRMS): Approximately 85% of cases
Secondary progressive MS (SPMS)
Primary progressive MS (PPMS)
Progressive-relapsing MS (PRMS)
The following 2 subgroups are sometimes included in RRMS:
Clinically isolated syndrome (CIS): A single episode of neurologic symptoms
Benign MS: MS with almost complete remission between relapses and little if any accumulation of physical disability over time
See Workup for more detail.
Treatment of MS has 2 aspects: immunomodulatory therapy (IMT) for the underlying immune disorder and therapies to relieve or modify symptoms.
Treatment of acute relapses is as follows:
Methylprednisolone (Solu-Medrol) can hasten recovery from an acute exacerbation of MS
Plasma exchange (plasmapheresis) can be used short term for severe attacks if steroids are contraindicated or ineffective 
Dexamethasone is commonly used for acute transverse myelitis and acute disseminated encephalitis
Most of the disease-modifying agents for MS (DMAMS) have been approved for use only in relapsing forms of MS. The DMAMS currently approved for use by the US Food and Drug Administration (FDA) include the following:
Interferon beta-1a (Avonex, Rebif) 
Interferon beta-1b (Betaseron, Extavia) 
Peginterferon beta-1a (Plegridy) 
Glatiramer acetate (Copaxone) 
Natalizumab (Tysabri) [10, 11]
Fingolimod (Gilenya) 
Teriflunomide (Aubagio) 
Dimethyl fumarate (Tecfidera) [15, 16, 17, 18]
Alemtuzumab (Lemtrada) [19, 20, 21]
A single-use autoinjector is also available for self-injection of interferon beta-1a (Rebif) in patients with relapsing forms of MS.
The following agents are used for treatment of aggressive MS:
High-dose cyclophosphamide (Cytoxan) has been used for induction therapy
Mitoxantrone is approved for reducing neurologic disability and/or the frequency of clinical relapses in patients with SPMS, PRMS, or worsening RRMS
Treatment of the symptoms of MS involves both pharmacologic and nonpharmacologic measures. The following symptoms may be amenable to pharmacologic therapy:
Fatigue: Off-label treatments include amantadine, methylphenidate, and fluoxetine
Depression: Selective serotonin reuptake inhibitors are preferred
Spasticity: Baclofen is effective in most cases
Pain: Tricyclic antidepressants are first-line drugs for primary pain
Sexual dysfunction: Oral phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil, vardenafil)
Optic neuritis: Intravenous methylprednisolone may speed recovery
Multiple sclerosis (MS) is an immune-mediated inflammatory disease that attacks myelinated axons in the central nervous system (CNS), destroying the myelin and the axon in variable degrees. In most cases, the disease follows a relapsing-remitting pattern, with short-term episodes of neurologic deficits that resolve completely or almost completely. A minority of patients experience steadily progressive neurologic deterioration.
The cause of MS is not known, but it likely involves a combination of genetic susceptibility and a presumed nongenetic trigger (eg, viral infection, low vitamin D levels) that together result in a self-sustaining autoimmune disorder that leads to recurrent immune attacks on the CNS (see Etiology). Geographic variation in the incidence of MS (see Epidemiology) supports the probability that environmental factors are involved in the etiology.
MS is diagnosed on the basis of clinical findings and supporting evidence from ancillary tests, such as magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid examination. (See Workup.) Traditionally, MS could not be diagnosed after only a single symptomatic episode, as diagnosis required the occurrence of repeat clinical attacks suggesting the appearance of lesions separated in time and space; however, recent guidelines allow diagnosis of MS even with a first clinical episode as long as ancillary tests support separation of lesions in time or space.
A common misconception is that any attack of CNS demyelination means a diagnosis of acute MS. When a patient has a first attack of demyelination, the physician should not rush to diagnose MS, because the differential diagnosis includes a number of other diseases. For example, MS must be distinguished from other neuroinflammatory disorders (see DDx.)
Treatment consists of immunomodulatory therapy for the underlying immune disorder and management of symptoms, as well as nonpharmacologic treatments, such as physical and occupational therapy (see Treatment). In the United States, various disease-modifying agents for MS are currently approved for use in relapsing MS.
Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. In pathologic specimens, the demyelinating lesions of MS, called plaques (see the image below), appear as indurated areas—hence the term sclerosis.
Examination of the demyelinating lesions in the spinal cord and brain of patients with MS shows myelin loss, destruction of oligodendrocytes, and reactive astrogliosis, often with relative sparing of the axon cylinder. In some MS patients, however, the axon is also aggressively destroyed.
The location of lesions in the CNS usually dictates the type of clinical deficit that results. As neural inflammation resolves in MS, some remyelination occurs, but some recovery of function that takes place in a patient could be due to nervous system plasticity. MS is also characterized by perivenular infiltration of lymphocytes and macrophages, as demonstrated in the image below. Infiltration of inflammatory cells occurs in the parenchyma of the brain, brainstem, optic nerves, and spinal cord.
One of the earliest steps in lesion formation is the breakdown of the blood-brain barrier. Enhanced expression of adhesion molecules on the surface of lymphocytes and macrophages seems to underlie the ability of these inflammatory cells to penetrate the blood-brain barrier.
The elevated immunoglobulin G (IgG) level in the cerebrospinal fluid, which can be demonstrated by an oligoclonal band pattern on electrophoresis, suggests an important humoral (ie, B-cell activation) component to MS. In fact, variable degrees of antibody-producing plasma cell infiltration have been demonstrated in MS lesions. The image below provides an overview of demyelination.
Immune cells in MS
Molecular studies of white matter plaque tissue have shown that interleukin (IL)-12, a potent promoter of inflammation, is expressed at high levels in lesions that form early in MS. B7-1, a molecule required to stimulate lymphocytes to release proinflammatory cytokines, is also expressed at high levels in early MS plaques. Evidence exists of elevated frequencies of activated myelin-reactive T-cell clones in the circulation of patients with relapsing-remitting MS and higher IL-12 production in immune cells of patients with progressive MS.
Decreased function of T-lymphocytes with a regulatory role (Tregs) has been implicated in MS. These Tregs are CD4+ CD25+ T cells that can be identified by their expression of a transcription factor known as Foxp3.
Conversely, the cytokine IL-23 has been shown to drive cells to commit to a pathogenic phenotype in autoimmune diseases, including MS. These pathogenic CD4+ T cells act reciprocally to counteract Treg function and can be identified by their high expression of the proinflammatory cytokine IL-17; they are therefore referred to as TH 17 cells.
Tregs and TH 17 cells are not the only critical immune cells in the pathogenesis of MS. Immune cells such as microglia (resident macrophages of the CNS), dendritic cells, natural killer (NK) cells, and B cells are gaining increased attention by MS researchers. In addition, nonimmune cells (ie, endothelial cells) have also been implicated in mechanisms that lead to CNS inflammation.
Approximately 55-75% of patients with MS have spinal cord lesions at some point during the course of the disease. Spinal MS is often associated with concomitant brain lesions; however, as many as 20% of patients with spinal lesions do not have intracranial plaques. No strong correlation has been established between the extent of the plaques and the degree of clinical disability.
Spinal MS has a predilection for the cervical spinal cord (67% of cases), with preferential, eccentric involvement of the dorsal and lateral areas of the spinal cord abutting the subarachnoid space around the cord. The gray matter may be involved.
Optic neuritis in MS
Approximately 20% of patients with MS present with optic neuritis (ON) as a first demyelinating event, and 40% of patients may experience ON during the course of their disease. Sequential episodes of optic nerve involvement and a longitudinally extensive myelopathy suggest a separate disorder, known as neuromyelitis optica [NMO], or Devic disease (see the images below). Although Devic disease is sometimes categorized as an MS variant, typical MS therapies are ineffective in Devic disease, and most experts consider Devic disease to be separate from MS.
The cause of MS is unknown, but it is likely that multiple factors act in concert to trigger or perpetuate the disease. It has been hypothesized that MS results when an environmental agent or event (eg, viral or bacterial infection, exposure to chemicals, lack of sun exposure) acts in concert with a genetic predisposition to immune dysfunction.
Genetic and molecular factors
The concordance rate for MS among monozygotic twins is only 20-35%, suggesting that genetic factors have only a modest effect. The presence of predisposing non-Mendelian factors (ie, epigenetic modification in 1 twin), along with environmental effects, plays an important role. For first-degree family members (children or siblings) of people affected with MS, the risk of developing the disorder is sevenfold higher than in the general population, but familial excess lifetime risk is only 2.5–5%.
Different variants of genes normally found in the general population, commonly referred to as polymorphisms, may lead to different gradations of cellular expression of those genes and therefore of the proteins that they encode. With MS susceptibility, it may be that a polymorphism within the promoter region of a gene involved in immune reactivity generates an exaggerated response (eg, elevated expression of a proinflammatory gene) to a given antigen, leading to uncontrolled immune cell proliferation and autoimmunity.
Research on single-nucleotide polymorphisms (SNPs) that confer risk of more severe disease or of developing particular forms of MS will be of great interest to the clinicians treating this complex disorder in the early stages. To date, however, HLA-DRB1 is the only chromosomal locus that has been consistently associated with MS susceptibility. Multiple other polymorphisms that may act in concert to predispose to MS have been described with genome-wide approaches, but their individual contribution to risk is not nearly as high as the risk conferred by the HLA locus.
Genes that instead of conferring susceptibility to MS confer relative protection against it are also being investigated, and clues are emerging from within the major histocompatibility complex (MHC) region. For example, it has been suggested that the HLA-C*05 allele confers protection against MS. )
Molecular mimicry has been proposed as an etiologic process in MS. The molecular mimicry hypothesis refers to the possibility that T cells in the peripheral blood may become activated to attack a foreign antigen and then erroneously direct their attack toward brain proteins that share similar epitopes.
Another hypothesis is that a virus may infect the immune system, activating self-reactive T cells (myelin reactive) that would otherwise remain quiescent. A virus that infects cells of the immune and nervous systems can possibly be reactivated periodically and thus lead to acute exacerbations in MS.
Epstein-Barr virus (EBV) infection has been found to become periodically reactivated, but a possible causative role in MS has been difficult to prove. Evidence supporting EBV infection as an etiologic factor includes (1) long-term studies showing a higher association with MS in individuals with early presence of serum antibodies against specific EBV antigens and (2) high expression of EBV antigens within MS plaques.
Evidence that argues against an etiologic role for EBV infection includes the fact that MS is a highly heterogeneous disease; EBV might help trigger some cases but not others, making associations in populations difficult. In addition, it is possible that EBV reactivation is an effect rather than a cause (ie, instead of viral reactivation being the trigger for MS, reactivation might be an epiphenomenon of a dysregulated immune system).
Geography is clearly an important factor in the etiology of MS. The incidence of the disease is lower in the equatorial regions of the world than in the southernmost and northernmost regions. However, a systematic review by Alonso and Hernán found that this latitude gradient became attenuated after 1980, apparently due to an increased incidence of MS in lower latitudes.
Apparently, whatever environmental factor is involved must exert its effect in early childhood. If an individual lives in an area with low incidence of MS until age 15 years, that person's risk remains low even if the individual subsequently moves to an area of high incidence.
On the other hand, certain ethnic groups (eg, Eskimos), despite living in areas of higher incidence, do not have a high frequency of MS. Therefore, the exact role played by geography versus genetics is not clear.
Vitamin D levels
Low levels of vitamin D have been proposed as one environmental factor contributing to the development of MS. Vitamin D has a role in regulating immune response, by decreasing production of proinflammatory cytokines and increasing production of anti-inflammatory cytokines; also, high circulating levels of vitamin D appear to be associated with a reduced risk of MS.
Thus, lower vitamin D levels due to lower sunlight exposure at higher latitudes may be one reason for the geographic variations in MS incidence, and the protective effect of traditional diets high in vitamin D could help explain why certain areas (eg, Norway) have a lower incidence of MS despite having limited sunlight. This hypothesis would also provide an explanation for the correlation between childhood sun exposure and MS in monozygotic twins discordant for MS.
Chronic cerebrospinal venous insufficiency
A controversial hypothesis proposes a vascular rather than an immunologic cause for some cases of MS. In 2008, Paolo Zamboni described an association between MS and chronic cerebrospinal venous insufficiency (CCSVI).
The CCSVI hypothesis posits that stenosis of the main extracranial venous outflow pathways results in compromised drainage and a high rate of cerebral venous reflux. The CCSVI hypothesis has been linked with the potential effects of iron deposition in the brain parenchyma, which some authors suggest is modestly to strongly predictive of disability progression, lesion volume accumulation, and atrophy in some patients with MS.[37, 38]
A small, open-label study suggested that internal jugular vein and azygous vein angioplasty had a positive effect on MS symptoms in patients with CCSVI. A meta-analysis found a positive association between CCSVI and MS, but poor reporting of the success of blinding and marked heterogeneity among studies of CCSVI precluded definitive conclusions.
Because of the potential danger of such experimental procedures in treating this unproven vascular condition, the US Food and Drug Administration (FDA) has issued a warning. See FDA issues alert on potential dangers of unproven treatment for multiple sclerosis.
Given the paucity of supporting evidence, most MS experts also question the CCSVI hypothesis and do not recommend this therapy. Nevertheless, CCSVI has received widespread attention in the lay press and MS support groups, so physicians should be prepared for inquiries from patients on this highly controversial subject.
Hepatitis B vaccine
Worldwide anecdotal reports suggesting a connection between hepatitis B vaccination and MS prompted the US Centers for Disease Control and Prevention (CDC) to investigate this possibility. The CDC concluded that the weight of the available scientific evidence does not support the suggestion that hepatitis B vaccine causes or worsens MS.
On the basis of the CDC findings, a National Multiple Sclerosis Society expert panel concluded as follows: “ People with MS should not be denied access to health-preserving and potentially-life saving vaccines because of their MS, and should follow the CDC guidelines for any given vaccine.”
United States statistics
Prevalence estimates for MS in the United States vary from 58 to 95 per 100,000 population. According to the National Multiple Sclerosis Society, 400,000 individuals in the United States are affected by MS. Misdiagnosis is common, however.
As is true of autoimmune diseases in general, MS is more common in women. The female-to-male ratio of MS incidence has increased since the mid-20th century, from an estimated 1.4 in 1955 to 2.3 in 2000. MS is usually diagnosed in persons aged 15-45 years; however, it can occur in persons of any age. The average age at diagnosis is 29 years in women and 31 years in men.
Worldwide, approximately 2.1 million people are affected by MS. The disease is seen in all parts of the world and in all races, but rates vary widely. In general, the prevalence of MS tends to increase with latitude (eg, lower rates in the tropics, higher rates in northern Europe), but there are many exceptions to this gradient (eg, low rates among Chinese, Japanese, and African blacks; high rates among Sardinians, Parsis, and Palestinians).
The presence of these exceptions implies that racial and ethnic differences affect risk. In addition, a substantial increase in MS incidence has been reported from different regions, suggesting that environmental factors, as well as geographic and genetic ones, play an important role in MS. (See Etiology.)
Epidemiologic studies indicate an increase in MS prevalence in Latin America. Susceptibility to MS and clinical behavior of the disease varies genetically in Latin America; for example, MS apparently does not occur in Amerindians with Mongoloid genes.
If left untreated, more than 30% of patients with MS will develop significant physical disability within 20-25 years after onset. Several of the disease-modifying agents used in MS have slowed disability progression within the duration of research trials; whether these effects will be maintained over longer periods is not known.
Less than 5-10% of patients have a clinically milder MS phenotype, in which no significant physical disability accumulates despite the passage of several decades after onset (sometimes in spite of multiple new lesions seen on MRI). Detailed examination of these patients in many instances reveals some degree of cognitive deterioration.
Male patients with primary progressive MS have the worst prognosis, with less favorable response to treatment and rapidly accumulating disability. The higher incidence of spinal cord lesions in primary progressive MS is also a factor in the rapid development of disability.
Life expectancy is shortened only slightly in persons with MS, and the survival rate is linked to disability. Death usually results from secondary complications (50-66%), such as pulmonary or renal causes, but can also be due to primary complications, suicide, and causes unrelated to MS. The Marburg variant of MS is an acute and clinically fulminant form of the disease that can lead to coma or death within days.
Patients should be educated on the purposes of medications, doses, and the management of adverse effects. Patients and caregivers need education on appropriate management of problems related to pain, fatigue, and spasticity, as well as on issues related to bowel, bladder, and sexual function. For patients with advanced disease, caregivers need hands-on training in transfer techniques, as well as in management of skin integrity, bowel programs, and urinary collection devices.
Patients with MS report a high incidence of falling. Contributing factors are similar to those in other populations with neurologic diseases. Patients with MS can benefit from receiving information about preventing falls from their healthcare practitioner.
To ensure a successful outcome, family members and caregivers should be included in any education provided. Community agencies, such as the state chapters of the National Multiple Sclerosis Society, can provide valuable information concerning community resources, as well as social support and education.
Patients may benefit from referral to comprehensive and professional organizations and Web sites that are dedicated to MS. Among these, the National Multiple Sclerosis Society is highly recommended for information on current hypotheses, ongoing research, general resources, and educational programs. Other highly recommended MS-related Web sites include MultipleSclerosis.com and The Consortium of Multiple Sclerosis Centers.
For patient education information, see the Brain & Nervous System Center.
Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec. 58(6):840-6. [Medline].
Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983 Mar. 13(3):227-31. [Medline].
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. 1996 Apr. 46(4):907-11. [Medline].
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. 2001 Jul. 50(1):121-7. [Medline].
Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011 Jan 18. 76(3):294-300. [Medline]. [Full Text].
Sanford M, Lyseng-Williamson KA. Subcutaneous recombinant interferon-ß-1a (Rebif®): a review of its use in the treatment of relapsing multiple sclerosis. Drugs. 2011 Oct 1. 71(14):1865-91. [Medline].
Betaseron [package insert]. Montville, NJ: Bayer Healthcare Pharmaceuticals Inc. May 2010.
Calabresi PA, Kieseier BC, Arnold DL, Balcer LJ, Boyko A, Pelletier J, et al. Pegylated interferon ß-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol. 2014 Jul. 13(7):657-65. [Medline].
Copaxone [package insert] [package insert]. North Wales, PA: Teva Pharmaceuticals USA. February 2009.
Pucci E, Giuliani G, Solari A, et al. Natalizumab for relapsing remitting multiple sclerosis. Cochrane Database Syst Rev. 2011 Oct 5. CD007621. [Medline].
Tysabri [package insert]. South San Francisco, CA: Biogen Idec Inc. 2011.
Novantrone [package insert]. Rockland, MA: Serono, Inc. May 2012.
Gilenya [package insert]. East Hanover, NJ: Novartis. September 2010.
Aubagio (teriflunomide) [package insert]. Cambridge, MA: Genentech Corp. September, 2012. Available at [Full Text].
Jeffrey S. FDA approves third oral agent for MS. March 27, 2013. Medscape Medical News. Available at http://www.medscape.com/viewarticle/781450. Accessed: April 2, 2013.
US Food and Drug Administration. FDA approves new multiple sclerosis treatment: Tecfidera. March 27, 2013. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345528.htm. Accessed: April 2, 2013.
Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012 Sep 20. 367(12):1098-107. [Medline]. [Full Text].
Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012 Sep 20. 367(12):1087-97. [Medline]. [Full Text].
Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24. 380(9856):1819-28. [Medline].
Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24. 380(9856):1829-39. [Medline].
Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, et al. Alemtuzumab more effective than interferon ß-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012 Apr 3. 78(14):1069-78. [Medline].
Jeffrey S. FDA Approves Interferon Autoinjector for MS. Available at http://www.medscape.com/viewarticle/777065. Accessed: February 20, 2013.
Windhagen A, Newcombe J, Dangond F, et al. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med. 1995 Dec 1. 182(6):1985-96. [Medline]. [Full Text].
Huan J, Culbertson N, Spencer L, et al. Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res. 2005 Jul 1. 81(1):45-52. [Medline].
Minagar A, Jy W, Jimenez JJ, et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology. 2001 May 22. 56(10):1319-24. [Medline].
Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005 Aug 15. 202(4):473-7. [Medline]. [Full Text].
Nielsen NM, Westergaard T, Rostgaard K, et al. Familial risk of multiple sclerosis: a nationwide cohort study. Am J Epidemiol. 2005 Oct 15. 162(8):774-8. [Medline].
Nischwitz S, Muller-Myhsok B, Weber F. Risk conferring genes in multiple sclerosis. FEBS Lett. 2011 Dec 1. 585(23):3789-97. [Medline].
Salvetti M, Giovannoni G, Aloisi F. Epstein-Barr virus and multiple sclerosis. Curr Opin Neurol. 2009 Jun. 22(3):201-6. [Medline].
Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology. 2008. 30(3):140-6. [Medline].
Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20. 296(23):2832-8. [Medline].
Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology. 2008. 30(3):140-6. [Medline].
Islam T, Gauderman WJ, Cozen W, Mack TM. Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology. 2007 Jul 24. 69(4):381-8. [Medline].
Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009 Apr. 80(4):392-9. [Medline]. [Full Text].
Zivadinov R, Schirda C, Dwyer MG, et al. Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case-control study. Int Angiol. 2010 Apr. 29(2):158-75. [Medline].
Study To Evaluate Treating Chronic Cerebrospinal Venous Insufficiency (CCSVI) in Multiple Sclerosis Patients. Available at http://clinicaltrials.gov/ct2/show/NCT01089686. Accessed: 10/4/2010.
Zamboni P, Galeotti R, Menegatti E, et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg. 2009 Dec. 50(6):1348-58.e1-3. [Medline].
Laupacis A, Lillie E, Dueck A, et al. Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a meta-analysis. CMAJ. 2011 Nov 8. 183(16):E1203-12. [Medline]. [Full Text].
Centers for Disease Control and Prevention. FAQs about Hepatitis B Vaccine (Hep B) and Multiple Sclerosis. [Full Text].
National Multiple Sclerosis Society. Vaccination. Available at http://www.nationalmssociety.org/living-with-multiple-sclerosis/healthy-living/vaccinations/index.aspx. Accessed: November 17, 2011.
National Multiple Sclerosis Society. Who Gets MS?. Available at http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/who-gets-ms/index.aspx. Accessed: 10/04/2010.
Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol Sci. 2001 Apr. 22(2):117-39. [Medline].
Aguirre-Cruz L, Flores-Rivera J, De La Cruz-Aguilera DL, Rangel-Lopez E, Corona T. Multiple sclerosis in Caucasians and Latino Americans. Autoimmunity. 2011 Nov. 44(7):571-5. [Medline].
Matsuda PN, Shumway-Cook A, Bamer AM, Johnson SL, Amtmann D, Kraft GH. Falls in multiple sclerosis. PM R. 2011 Jul. 3(7):624-32; quiz 632. [Medline].
Roodhooft JM. Ocular problems in early stages of multiple sclerosis. Bull Soc Belge Ophtalmol. 2009. 65-8. [Medline].
Braley TJ, Chervin RD. Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment. Sleep. 2010 Aug. 33(8):1061-7. [Medline].
Optic Neuritis Study Group. The clinical profile of optic neuritis. Experience of the Optic Neuritis Treatment Trial. Optic Neuritis Study Group. Arch Ophthalmol. 1991 Dec. 109(12):1673-8. [Medline].
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov. 33(11):1444-52. [Medline].
Lonergan R, Kinsella K, Duggan M, Jordan S, Hutchinson M, Tubridy N. Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?. Mult Scler. 2009 Dec. 15(12):1528-31. [Medline].
Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29. 338(5):278-85. [Medline].
Barkhof F, Filippi M, Miller DH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain. 1997 Nov. 120 ( Pt 11):2059-69. [Medline].
Bonhomme GR, Waldman AT, Balcer LJ, et al. Pediatric optic neuritis: brain MRI abnormalities and risk of multiple sclerosis. Neurology. 2009 Mar 10. 72(10):881-5. [Medline].
Filippi M. Enhanced magnetic resonance imaging in multiple sclerosis. Mult Scler. 2000 Oct. 6(5):320-6. [Medline].
Filippi M, Bozzali M, Horsfield MA, et al. A conventional and magnetization transfer MRI study of the cervical cord in patients with MS. Neurology. 2000 Jan 11. 54(1):207-13. [Medline].
Filippi M, Yousry TA, Alkadhi H, Stehling M, Horsfield MA, Voltz R. Spinal cord MRI in multiple sclerosis with multicoil arrays: a comparison between fast spin echo and fast FLAIR. J Neurol Neurosurg Psychiatry. 1996 Dec. 61(6):632-5. [Medline]. [Full Text].
Grossman RI, Barkhof F, Filippi M. Assessment of spinal cord damage in MS using MRI. J Neurol Sci. 2000 Jan 15. 172 Suppl 1:S36-9. [Medline].
Neema M, Goldberg-Zimring D, Guss ZD, et al. 3 T MRI relaxometry detects T2 prolongation in the cerebral normal-appearing white matter in multiple sclerosis. Neuroimage. 2009 Jul 1. 46(3):633-41. [Medline]. [Full Text].
Poonawalla AH, Hou P, Nelson FA, Wolinsky JS, Narayana PA. Cervical Spinal Cord Lesions in Multiple Sclerosis: T1-weighted Inversion-Recovery MR Imaging with Phase-Sensitive Reconstruction. Radiology. 2008 Jan. 246(1):258-264. [Medline].
Vaneckova M, Seidl Z, Krasensky J, et al. Patients' stratification and correlation of brain magnetic resonance imaging parameters with disability progression in multiple sclerosis. Eur Neurol. 2009. 61(5):278-84. [Medline].
Wattjes MP, Barkhof F. High field MRI in the diagnosis of multiple sclerosis: high field-high yield?. Neuroradiology. 2009 May. 51(5):279-92. [Medline].
[Guideline] Traboulsee, A. et al. Revised Recommendations of the CMSC Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-up of Multiple Sclerosis. Consortim of Multiple Sclerosis Centers. Available at http://c.ymcdn.com/sites/www.mscare.org/resource/collection/9C5F19B9-3489-48B0-A54B-623A1ECEE07B/MRIprotocol2015.pdf. Accessed: August 13, 2015.
Agosta F, Absinta M, Sormani MP, et al. In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study. Brain. 2007 Aug. 130:2211-9. [Medline].
Fazekas F, Offenbacher H, Fuchs S, et al. Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology. 1988 Dec. 38(12):1822-5. [Medline].
Colorado RA, Shukla K, Zhou Y, Wolinsky JS, Narayana PA. Multi-task functional MRI in multiple sclerosis patients without clinical disability. Neuroimage. 2012 Jan 2. 59(1):573-81. [Medline]. [Full Text].
Wang J, Xiao Y, Luo M, Zhang X, Luo H. Statins for multiple sclerosis. Cochrane Database Syst Rev. 2010 Dec 8. CD008386. [Medline].
Arnold DL, Matthews PM, Francis G, Antel J. Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 1990 Apr. 14(1):154-9. [Medline].
Henning A, Schar M, Kollias SS, Boesiger P, Dydak U. Quantitative magnetic resonance spectroscopy in the entire human cervical spinal cord and beyond at 3T. Magn Reson Med. 2008 Jun. 59(6):1250-8. [Medline].
Marliani AF, Clementi V, Albini-Riccioli L, Agati R, Leonardi M. Quantitative proton magnetic resonance spectroscopy of the human cervical spinal cord at 3 Tesla. Magn Reson Med. 2007 Jan. 57(1):160-3. [Medline].
Berg D, Maurer M, Warmuth-Metz M, Rieckmann P, Becker G. The correlation between ventricular diameter measured by transcranial sonography and clinical disability and cognitive dysfunction in patients with multiple sclerosis. Arch Neurol. 2000 Sep. 57(9):1289-92. [Medline].
Walter U, Wagner S, Horowski S, Benecke R, Zettl UK. Transcranial brain sonography findings predict disease progression in multiple sclerosis. Neurology. 2009 Sep 29. 73(13):1010-7. [Medline].
Vazquez-Marrufo M, Gonzalez-Rosa JJ, Vaquero E, et al. Quantitative electroencephalography reveals different physiological profiles between benign and remitting-relapsing multiple sclerosis patients. BMC Neurol. 2008 Nov 24. 8:44. [Medline]. [Full Text].
Jeffrey S. TOPIC: Teriflunomide Delays Clinically Definite MS. Medscape Medical News. Available at http://www.medscape.com/viewarticle/803177. Accessed: May 8, 2013.
Rodriguez M, Karnes WE, Bartleson JD, Pineda AA. Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology. 1993 Jun. 43(6):1100-4. [Medline].
Spelman T, Mekhael L, Burke T, Butzkueven H, Hodgkinson S, Havrdova E, et al. Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis. Eur J Neurol. 2016 Jan 19. [Medline].
Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology. 1993 Apr. 43(4):655-61. [Medline].
Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996 Mar. 39(3):285-94. [Medline].
Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet. 1998 Nov 7. 352(9139):1498-504. [Medline].
Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology. 2002 Nov 26. 59(10):1496-506. [Medline].
Schwid SR, Panitch HS. Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon beta-1a for relapsing multiple sclerosis. Clin Ther. 2007 Sep. 29(9):2031-48. [Medline].
Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995 Jul. 45(7):1268-76. [Medline].
Johnson KP, Brooks BR, Ford CC, et al. Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group. Mult Scler. 2000 Aug. 6(4):255-66. [Medline].
Khan O, Rieckmann P, Boyko A, Selmaj K, Zivadinov R. Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann Neurol. 2013 Jun. 73(6):705-13. [Medline].
Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2. 354(9):899-910. [Medline].
Cadavid D, Jurgensen S, Lee S. Impact of natalizumab on ambulatory improvement in secondary progressive and disabled relapsing-remitting multiple sclerosis. PLoS One. 2013. 8(1):e53297. [Medline]. [Full Text].
Chun J, Brinkmann V. A mechanistically novel, first oral therapy for multiple sclerosis: the development of fingolimod (FTY720, Gilenya). Discov Med. 2011 Sep. 12(64):213-28. [Medline].
Hughes S. Shorter washout reduces MS relapse switching off natalizumab. Medscape Medical News. October 7, 2013. [Full Text].
Hughes S. Shorter Washout Better for Natalizumab-to-Fingolimod Switch. Medscape Medical News. Available at http://www.medscape.com/viewarticle/822567. Accessed: April 1, 2014.
Cohen M, Maillart E, Tourbah A, De Sèze J, Vukusic S, Brassat D, et al. Switching From Natalizumab to Fingolimod in Multiple Sclerosis: A French Prospective Study. JAMA Neurol. 2014 Feb 24. [Medline].
O'Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011 Oct 6. 365(14):1293-303. [Medline].
Semedo, D. Aubagio (Teriflunomide) Slows Brain Atrophy in Patients with Relapsing Multiple Sclerosis. Multiple Sclerosis News Today. Available at http://multiplesclerosisnewstoday.com/2015/10/08/aubagio-teriflunomide-slows-brain-atrophy-patients-relapsing-multiple-sclerosis/. October 8, 2015; Accessed: October 14, 2015.
A study comparing the effectiveness and safety of teriflunomide and interferon beta-1a in patients with relapsing multiple sclerosis (TENERE). 4th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC)/Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). June 2, 2012 (ClinicalTrials.gov identifier: NCT00883337).
A multicenter double-blind parallel-group placebo-controlled study of the efficacy and safety of teriflunomide in patients with relapsing multiple sclerosis who are treated with interferon-beta. (ClinicalTrials.gov identifier: NCT01252355).
Fox EJ, Sullivan HC, Gazda SK, et al. A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis. Eur J Neurol. 2012 Feb. 19(2):307-11. [Medline].
Anderson P. Alemtuzumab Benefits Hard-to-Treat MS Patients. Medscape Medical News. Available at http://www.medscape.com/viewarticle/805173. Accessed: June 12, 2013.
Harrison DM, Gladstone DE, Hammond E, et al. Treatment of relapsing-remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance. Mult Scler. 2012 Feb. 18(2):202-9. [Medline].
Rojas JI, Romano M, Ciapponi A, Patrucco L, Cristiano E. Interferon beta for primary progressive multiple sclerosis. Cochrane Database Syst Rev. 2009 Jan 21. CD006643. [Medline].
Goodkin DE, Rudick RA, VanderBrug Medendorp S, et al. Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann Neurol. 1995 Jan. 37(1):30-40. [Medline].
Kappos L, Radue EW, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4. 362(5):387-401. [Medline].
Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4. 362(5):402-15. [Medline].
Khatri B, Barkhof F, Comi G, et al. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol. 2011 Jun. 10(6):520-9. [Medline].
Killestein J, Rudick RA, Polman CH. Oral treatment for multiple sclerosis. Lancet Neurol. 2011 Nov. 10(11):1026-34. [Medline].
Multiple Sclerosis Association of America (MSAA). MS Research Update. Available at http://mymsaa.org/PDFs/MSAA_Research_Update_2013.pdf. Accessed: March 27, 2013.
Kappos L, Li D, Calabresi PA, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011 Nov 19. 378(9805):1779-87. [Medline].
Anderson P. Myelin peptide skin patch safe, reduces MS activity. Medscape Medical News. July 29, 2013. [Full Text].
Walczak A, Siger M, Ciach A, Szczepanik M, Selmaj K. Transdermal application of myelin peptides in multiple sclerosis treatment. JAMA Neurol. 2013 Jul 1. 1-6. [Medline].
Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998 Jul 30. 339(5):285-91. [Medline].
Tsui A, Lee MA. Multiple sclerosis and pregnancy. Curr Opin Obstet Gynecol. 2011 Dec. 23(6):435-9. [Medline].
Krupp LB, Christodoulou C, Melville P, et al. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology. 2011 Apr 26. 76(17):1500-7. [Medline]. [Full Text].
Attarian HP, Brown KM, Duntley SP, Carter JD, Cross AH. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch Neurol. 2004 Apr. 61(4):525-8. [Medline].
MacAllister WS, Krupp LB. Multiple sclerosis-related fatigue. Phys Med Rehabil Clin N Am. 2005 May. 16(2):483-502. [Medline].
Solaro C, Uccelli MM. Management of pain in multiple sclerosis: a pharmacological approach. Nat Rev Neurol. 2011 Aug 16. 7(9):519-27. [Medline].
Goodman AD, Brown TR, Krupp LB, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28. 373(9665):732-8. [Medline].
Ampyra [package insert]. Hawthorne, NY: Acorda Therapeutics, Inc. 2010.
Nicholas RS, Friede T, Hollis S, Young CA. Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Database Syst Rev. 2009 Jan 21. CD004193. [Medline].
US Food and Drug Administration. FDA approves Botox to treat specific form of urinary incontinence. August 25, 2011. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269509.htm. Accessed: November 28, 2011.
Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27. 326(9):581-8. [Medline].
Myhr KM. Vitamin D treatment in multiple sclerosis. J Neurol Sci. 2009 Nov 15. 286(1-2):104-8. [Medline].
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. November 30, 2010. Available at http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed: December 29, 2011.
Summerday NM, Brown SJ, Allington DR, Rivey MP. Vitamin D and multiple sclerosis: review of a possible association. J Pharm Pract. 2012 Feb. 25(1):75-84. [Medline].
Jagannath VA, Fedorowicz Z, Asokan GV, Robak EW, Whamond L. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev. 2010 Dec 8. CD008422. [Medline].
DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol. 2003 Apr. 60(4):504-9. [Medline].
Confavreux C, Suissa S, Saddier P, Bourdès V, Vukusic S. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med. 2001 Feb 1. 344(5):319-26. [Medline].
Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011 Oct. 68(10):1267-71. [Medline].
Azasan [package insert] [package insert]. Wilmington, NC: Salix pharmaceuticals Inc. August 2011.
Cyclophosphamide [package insert]. Deerfield, IL: Baxter Healthcare Corporation. June 2004.
Brooks M. New AAN guideline on psychiatric disorders in MS. Medscape Medical News. January 3, 2014. [Full Text].
Hughes S. New Test to Identify PML Risk With Natalizumab in MS. Medscape Medical News. Available at http://www.medscape.com/viewarticle/832504. Accessed: October 7, 2014.
Jeffrey S. No Cognitive Disadvantage in Pediatric- vs Adult-Onset MS. Medscape Medical News. Available at http://www.medscape.com/viewarticle/831536. Accessed: September 15, 2014.
Keller DM. Fingolimod Reduces Annual Brain Volume Loss in MS. Medscape Medical News. Jun 6 2014. [Full Text].
Minden SL, Feinstein A, Kalb RC, Miller D, Mohr DC, Patten SB, et al. Evidence-based guideline: Assessment and management of psychiatric disorders in individuals with MS: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013 Dec 27. [Medline].
Rovira À, Wattjes MP, Tintoré M, Tur C, Yousry TA, Sormani MP, et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process. Nat Rev Neurol. 2015 Aug. 11 (8):471-82. [Medline].
[Guideline] Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence: A Consensus Paper. The Consortium of Multiple Sclerosis Centers. Available at http://www.mscare.org/?page=dmt. July 2014;
[Guideline] Filippi M, Rocca A, Arnold DL, Bakshi R, Barkhof F, De Stefano N, et al. Use of Imaging in Multiple Sclerosis. Gilhus NE, Barnes MP, Brainin M. European Handbook of Neurological Management. 2nd ed. Oxford (UK): Wiley-Blackwell; 2011. Vol 1: 35-51.
Wattjes MP, Rovira À, Miller D, Yousry TA, Sormani MP, de Stefano MP, et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis--establishing disease prognosis and monitoring patients. Nat Rev Neurol. 2015 Oct. 11 (10):597-606. [Medline].
Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, et al. Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2015 Oct 8. 373 (15):1418-28. [Medline]. [Full Text].
Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Jun 22. 381 (9884):2167-75. [Medline].
|Clinical Presentation||Additional Data Needed for MS Diagnosis|
||None; clinical evidence will suffice. Additional evidence (eg, brain MRI) desirable,
but must be consistent with MS
||Dissemination in space demonstrated by MRI or
Await further clinical attack implicating a different site
||Dissemination in time demonstrated by
MRI or second clinical attack
||Dissemination in space demonstrated by
MRI or await a second clinical attack implicating a different CNS site
Dissemination in time, demonstrated by MRI or second clinical attack
|· Insidious neurologic progression suggestive of MS||One year of disease progression and dissemination in space, demonstrated by 2 of the following:
|Notes: An attack is defined as a neurologic disturbance of the kind seen in MS. It can be documented by subjective report or by objective observation, but it must last for at least 24 hours. Pseudoattacks and single paroxysmal episodes must be excluded. To be considered separate attacks, at least 30 days must elapse between onset of one event and onset of another event.|