eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases

Multiple Sclerosis

Author: Fernando Dangond, MD, Senior Director of Medical Affairs, Neurology, EMD Serono, Inc
Contributor Information and Disclosures

Updated: Sep 11, 2009

Introduction

Background

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). MS lesions, characterized by perivascular infiltration of monocytes and lymphocytes, appear as indurated areas in pathologic specimens; hence, the term sclerosis in plaques.

MS is a dynamic disease, with almost constant lesion formation and a progressive clinical course leading to physical disability. For every 8-10 new lesions detected on magnetic resonance imaging (MRI), only one clinical manifestation typically can be demonstrated. Patients with relapsing remitting MS have an average of 5-10 new lesions per year and 1 or 2 clinical exacerbations.1

With the advent of MRI, the ability to confirm the diagnosis of MS has improved dramatically. MRI characteristically shows lesions of high T2 signal intensity of variable location in the white matter of the brain, brain stem, optic nerves, or spinal cord. In typical cases, the lesions tend to occur in periventricular areas and may occur in the corpus callosum. Newer MRI techniques (eg, magnetization transfer ratio [MTR], fluid attenuated inversion recovery [FLAIR], magnetic resonance spectroscopy [MRS]) promise to yield important information regarding MS heterogeneity, prognosis, and treatment effects.

Despite intensive efforts in finding the source of the disease, no etiologic agent for MS has been identified. The disease presumably can be exacerbated by hormonal changes during the postpartum period. Some argue that MS could be a heterogeneous disorder triggered or perpetuated by several different environmental agents. In fact, only 1 of every 4 MS attacks is associated with an intercurrent infection.

The disease can present in different forms, such as primary progressive, relapsing remitting, relapsing progressive, and secondary progressive phenotypes. Genetic susceptibility factors may play a role, as the disease is more common in Caucasian populations living in northern latitudes. This susceptibility may be part of a complex and heterogeneous group of genetic and epigenetic factors that have an impact, along with environmental factors, on the initiation and maintenance of disease. In addition, migration to high-risk areas before 15 years of age seems to increase the risk of developing MS, lending further support to the environmental factor hypothesis.

For related information, see Medscape's Multiple Sclerosis Resource Center.

Pathophysiology

Multiple sclerosis is characterized by perivenular infiltration of lymphocytes and macrophages in the parenchyma of the brain, brain stem, optic nerves, and spinal cord. Expression of adhesion molecules on the surface 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 (CSF), 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 (depicted in Media file 1).

The mechanism of demyelination in multiple sclero...

The mechanism of demyelination in multiple sclerosis may be activation of myelin-reactive T cells in the periphery, which then express adhesion molecules, allowing their entry through the blood-brain barrier (BBB). T cells are activated following antigen presentation by antigen-presenting cells such as macrophages and microglia, or B cells. Perivascular T cells can secrete proinflammatory cytokines, including interferon gamma and tumor necrosis factor alpha. Antibodies against myelin also may be generated in the periphery or intrathecally.

Ongoing inflammation leads to epitope spread and recruitment of other inflammatory cells (ie, bystander activation). The T cell receptor recognizes antigen in the context of human leukocyte antigen molecule presentation and also requires a second event (ie, co-stimulatory signal via the B7-CD28 pathway, not shown) for T cell activation to occur. Activated microglia may release free radicals, nitric oxide, and proteases that may contribute to tissue damage.

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The mechanism of demyelination in multiple sclero...

The mechanism of demyelination in multiple sclerosis may be activation of myelin-reactive T cells in the periphery, which then express adhesion molecules, allowing their entry through the blood-brain barrier (BBB). T cells are activated following antigen presentation by antigen-presenting cells such as macrophages and microglia, or B cells. Perivascular T cells can secrete proinflammatory cytokines, including interferon gamma and tumor necrosis factor alpha. Antibodies against myelin also may be generated in the periphery or intrathecally.

Ongoing inflammation leads to epitope spread and recruitment of other inflammatory cells (ie, bystander activation). The T cell receptor recognizes antigen in the context of human leukocyte antigen molecule presentation and also requires a second event (ie, co-stimulatory signal via the B7-CD28 pathway, not shown) for T cell activation to occur. Activated microglia may release free radicals, nitric oxide, and proteases that may contribute to tissue damage.


Molecular studies of the white matter plaque tissue have shown that interleukin (IL)–12, a potent proinflammatory substance, is expressed at high levels in early-formed lesions. A molecule required to stimulate lymphocytes to release proinflammatory cytokines, B7-1, is also expressed at high levels in early MS plaques. Evidence exists of higher 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, when compared with healthy controls.

Recently, decreased function of immune cells 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, hence being referred to as T H 17 cells. Tregs and T H 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.2

The favorable clinical responses to the disease-modifying immunomodulatory agents (ie, interferon beta-1a and beta-1b, glatiramer acetate) suggest that these medications modify disease progression, at least in part, based on their ability to counteract the proinflammatory phenotype of immune cells. Other disease-modifying treatments for MS include mitoxantrone (a DNA intercalator that affects lymphocyte counts) and natalizumab (a monoclonal antibody against the adhesion molecule VLA-4 that prevents migration of immune cells to the CNS). The exact mechanisms leading to the efficacy of all these agents are unknown.

MS is a complex and heterogeneous disease, and our understanding of the disease initiation mechanism and its wide clinical variability is limited.

Frequency

United States

In the United States, multiple sclerosis has a prevalence of nearly 400,000 cases, and approximately 10,000 people are newly diagnosed with this disease every year.3

International

More than 2.5 million people worldwide are estimated to be affected by multiple sclerosis.3

Mortality/Morbidity

Multiple sclerosis causes considerable disability in the working age group. People with MS usually die of complications rather than of MS itself, including recurrent infections (especially in bedridden patients). Patients with MS are thought to have an average life expectancy 5-7 years shorter than that of the general population.

Race

Multiple sclerosis presents more often in populations of northern European ancestry. Disease severity or drug treatment effect variability may be accounted for, at least in part, by racial or geographic differences.

Sex

Multiple sclerosis affects females more than males (1.6-2:1), but the basis for this difference is unknown. This ratio is even higher (3:1) among patients in whom onset of MS is before age 15 years or after age 50 years, suggesting a hormonal component to the disease process. Males have a greater tendency to develop primary progressive MS, while females tend to experience more relapses.

Age

Multiple sclerosis most commonly afflicts people aged 18-50 years, but any age group can be affected.

Clinical

History

Attacks or exacerbations of multiple sclerosis are characterized by new symptoms that reflect CNS involvement. These symptoms are typically separated in time (eg, by months or years) and in anatomical location (eg, weakness of one or more limbs, optic neuritis, sensory symptoms). Recognizing that physical and cognitive disability progression in MS may occur in the absence of clinical exacerbations is important.

  • Patients who improve after acute attacks have relapsing remitting MS (RRMS). However, during the natural course of RRMS, approximately 75-85% of patients enter a stage referred to as secondary progressive MS (SPMS).
  • Patients with primary progressive MS (PPMS) tend to accumulate disability without interruption (ie, without remissions) from the time of disease onset. Some of these patients first present with weakness of only one limb, which gradually progresses to involve other limbs and may culminate in total paralysis. Patients with PPMS typically respond poorly to the current therapeutic options for MS, accumulate disability faster than other patients, and tend to have more weakness of the legs as well as incontinence (a reflection of greater spinal cord involvement).
  • Patients who have RRMS but accumulate disability between and during attacks can be defined as having relapsing progressive disease (RPMS).
  • Although most patients have a wide range of symptoms from lesions in different areas of the brain and spinal cord, others may present with predominantly visual, cognitive, or cerebellar symptoms.
  • Patients with MS are now thought to reach a clinical threshold (itself a reflection of immune system dysfunction and axonal involvement), after which deterioration occurs in a continuous course and ominous MRI signs become more apparent (eg, T1 hypointensities, brain atrophy). These T1 "holes" (ie, T1 hypointensities that become permanent) and signs of brain or spinal cord atrophy are indicative of a neurodegenerative process, indicating that MS is not only an inflammatory disease. The clinical history often reflects these processes, as patients may report short-term memory problems, difficulty executing sequential tasks, or visuospatial disturbances.

    Keep in mind, however, that every patient with MS presents differently, with some exhibiting severe cognitive decline in the absence of widespread inflammation or atrophy by MRI and others performing well in cognitive tests despite the presence of numerous MRI lesions. The exact correlation of MRI findings with clinical outcome in MS is still unknown, and efforts to develop composite MRI indexes that allow better disease monitoring are underway.
  • Use of the term benign MS should be discouraged, since almost all patients have relentless progression of the disease, even in the absence of clinical attacks. Not uncommonly, detailed examination of a patient with so-called benign MS encounters clear evidence of short-term memory difficulties, cognitive dysfunction, or brain atrophy on MRI of the head. In the author's view, the use of the term benign MS should be reserved for retrospective assessments of clinical course, as only a minority of patients end up having this form. The prospective use of the term benign MS leads to false expectations of disease outcome by the patients and their relatives, improper counseling, and inappropriate delay of treatment with disease-modifying drugs.
  • Patients with MS tend to experience variable degrees of fatigue. This symptom is typically described as either physical exhaustion or mental/cognitive slowing. It must be differentiated from depression (which may, however, coexist), lack of sleep, and exertional exhaustion due to disability. Patients may feel particularly fatigued after taking a hot shower or after strenuous activity in heated environments. Heat exposure may also lead to episodes of optic nerve dysfunction (ie, Uhthoff phenomenon), the mechanisms of which remain poorly understood.
  • MS may present in an acute and clinically fulminant form (termed Marburg variant of MS), which can lead to coma or death or may present with concomitant optic nerve involvement and a longitudinally extensive myelopathy (ie, neuromyelitis optica [NMO] or Devic disease, considered by some to be an MS variant). NMO can now be confirmed by the presence of serum antibodies against aquaporin 4, a water channel expressed at major fluid-tissue barriers across the CNS.4
  • MS must also be distinguished from other neuroinflammatory disorders, including acute disseminated encephalomyelitis (ADEM), Schilder disease, and Baló concentric sclerosis.
    • ADEM is considered an isolated postinfectious or postvaccinial autoimmune attack on the CNS that leads to diffuse demyelination. It is often devastating and occasionally has a fulminant hemorrhagic component (in which case it is termed acute hemorrhagic encephalomyelitis or leukoencephalitis of Weston Hurst).
    • Schilder disease is characterized in children and young adolescents by massive demyelination, presenting often as asymmetrical foci (often the size of an entire lobe) in the white matter on MRI and presenting with a malignant course (ie, deterioration over months or a few years with cortical blindness, hemiplegia, or paraplegia). Some patients, however, may respond to steroids and immunosuppressive therapy.
    • Baló concentric sclerosis is considered by some authors to be a variant of Schilder disease, with MRI lesions showing a characteristic alternating pattern of spared and damaged white matter that suggests progression of the disease process from the ventricles outward. Baló disease is often associated with a more inflammatory CSF and a more fulminant progression than typical MS.
  • MS may present in various forms. Some patients have a predominance of cognitive changes, while others present with prominent ataxia, hemiparesis or paraparesis, depression, or visual symptoms. Bipolar disorder and frank dementia may appear late in the disease course, but sometimes are found at the time of initial diagnosis. Symptoms can be exacerbated by intercurrent illness, including viral or bacterial upper respiratory or urinary tract infections. Trauma has no impact on disease exacerbation. The impact of emotional stress on exacerbations is probably minimal and remains controversial.
  • Optic neuritis presents clinically as orbital pain, at rest or during eye movement, and loss of vision. Patients may complain of "patchy loss of vision," and upon examination, a cecocentral scotoma and an afferent pupillary defect may be found. Patients may experience color desaturation even with normal visual acuity, usually manifested as the perception of red color as different shades of orange or gray.
  • Patients with MS may present with facial palsies or trigeminal neuralgia. In fact, the presence of bilateral facial weakness or trigeminal neuralgia strongly suggests the diagnosis of MS. Facial myokymia may also be a presenting symptom. Nystagmus (direction-changing) and internuclear ophthalmoplegia signs are other manifestations.
  • Painful limb syndromes are important to recognize, as those with paroxysmal qualities may respond better to specific treatments. Patients with MS also commonly complain of numbness or tingling in one or more limbs, variable weakness, or sensory level-related symptoms. Some have difficulty describing weakness or numbness, as these symptoms are obscured by incapacitating fatigue.
  • Episodes of central (as opposed to peripheral) vertigo are not uncommon. The nystagmus accompanying central vertigo has a rapid onset, does not fatigue easily, and changes with direction of gaze. CNS vertigo is usually accompanied by other complaints that can be directly attributed to brainstem or cerebellar pathway involvement (eg, diplopia, dysarthria).
  • An often overlooked manifestation of MS is the pseudobulbar affect, whereby patients have difficulty controlling their emotions (laughing, crying) and are perceived to act inappropriately by coworkers or friends.
    • Behavioral/cognitive symptoms may also include social disinhibition, dementia, or depression.
    • A greater tendency for attempting and committing suicide in patients with MS is not related exclusively to a reactive depression, since this tendency is higher than that of patients with other devastating neurologic disorders such as chronic inflammatory demyelinating polyradiculopathy (CIDP).
    • The neurologist should be aware that patients with conversion reactions and inappropriate affect, such as la belle indifference, may on occasion have an underlying organic illness such as MS.
  • Urinary retention and incontinence are common. Bowel habit changes may occur, but bowel incontinence is less frequent.
  • Sexual dysfunction affects the great majority of patients with MS and includes symptoms such as lack of desire, erectile dysfunction, impaired sexual responsiveness, premature ejaculation, impaired genital sensation, or inability to physically interact with the partner due to painful leg adductor muscle spasms.

Physical

The Kurtzke Expanded Disability Status Scale (EDSS) is used as a measure of disease progression by assigning a severity score (0-10) to the patient's clinical status. Although the scale does not correspond linearly to common progression points for many patients, its widespread use and ease of implementation allow its use as a standardization measure for clinical trials.5

  • 0 - Normal neurologic examination (all grade 0 in functional systems [FS]; cerebral grade 1 acceptable)
  • 1 - No disability, minimal signs in one FS (ie, one grade 1 excluding cerebral grade 1)
  • 1.5 - No disability, minimal signs in more than one FS (more than one grade 1 excluding cerebral grade 1)
  • 2.0 - Minimal disability in one FS (one FS grade 2, others 0 or 1)
  • 2.5 - Minimal disability in two FS (two FS grade 2, others 0 or 1)
  • 3.0 - Moderate disability in one FS (one FS grade 3, others 0 or 1), or mild disability in three or four FS (three or four FS grade 2, others 0 or 1)
  • 3.5 - Fully ambulatory but with moderate disability in one FS (one grade 3 and one or two FS grade 2) or two FS grade 3, others 0 or 1, or five FS grade 2, others 0 or 1
  • 4.0 - Fully ambulatory without aid, self-sufficient, up and about some 12 hours a day despite relatively severe disability consisting of one FS grade 4 (others 0 or 1), or combinations of lesser grades exceeding limits of previous steps; able to walk without aid or rest some 500 meters (0.3 miles)
  • 4.5 - Fully ambulatory without aid, up and about much of the day, able to work a full day, may otherwise have some limitation of full activity or require minimal assistance; characterized by relatively severe disability, usually consisting of one FS grade 4 (others 0 or 1) or combinations of lesser grades exceeding limits of previous steps; able to walk without aid or rest for some 300 meters (975 ft)
  • 5.0 - Ambulatory without aid or rest for about 200 meters (650 feet); disability severe enough to impair full daily activities (eg, to work a full day without special provisions); usual FS equivalents are one grade 5 alone, others 0 or 1, or combinations of lesser grades usually exceeding specifications for step 4.0
  • 5.5 - Ambulatory without aid or rest for about 100 meters (325 ft); disability severe enough to impair full daily activities; usual FS equivalents are one grade 5 alone, others 0 or 1, or combinations of lesser grades usually exceeding specifications for step 4.0
  • 6.0 - Intermittent or constant unilateral assistance (cane, crutch, brace) required to walk about 100 meters (325 ft) with or without resting; usual FS equivalents are combinations with more than two FS grade 3+
  • 6.5 - Constant bilateral assistance (canes, crutches, braces) required to walk about 20 meters (65 ft); usual FS equivalents are combinations with more than two FS grade 3+
  • 7.0 - Unable to walk beyond about 5 meters (16 ft) even with aid, essentially restricted to wheelchair; wheels self in standard wheelchair a full day and transfers alone; up and about in wheelchair some 12 hours a day; usual FS equivalents are combinations with more than one FS grade 4+; very rarely pyramidal grade 5 alone
  • 7.5 - Unable to take more than a few steps; restricted to wheelchair; may need aid in transfers, wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair; usual FS equivalents are combinations with more than one FS grade 4+
  • 8.0 - Essentially restricted to bed or chair or perambulated in wheelchair; but may be out of bed much of the day; retains many self-care functions; generally has effective use of arms; usual FS equivalents are combinations, generally grade 4+ in several systems
  • 8.5 - Essentially restricted to bed for much of the day; has some effective use of arm(s); retains some self-care functions; usual FS equivalents are combinations, generally grade 4+ in several systems
  • 9.0 - Helpless bed patient; can communicate and eat; usual FS equivalents are combinations, mostly grade 4
  • 9.5 - Totally helpless bed patient; unable to communicate effectively or eat/swallow; usual FS equivalents are combinations, almost all grade 4+
  • 10 - Death due to MS

Causes

The cause of multiple sclerosis is unknown. Multiple factors (not a single identifiable agent or event) likely act in concert to trigger or perpetuate MS. These factors are in part environmental and in part hereditary (genes are thought to have a modest effect).

  • An environmental agent or event (eg, virus, bacteria, chemicals, lack of sun exposure) has been hypothesized to act in concert with a specific genetic predisposition (ie, a set of genes or polymorphisms) to result in immune dysfunction. For instance, 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, thus, of the proteins that they encode. Therefore, an individual with a polymorphism within the promoter region of a gene that is involved in immune reactivity may hypothetically generate an exaggerated response (eg, elevated gene expression of a proinflammatory gene) to a given antigen, leading to uncontrolled immune cell proliferation and autoimmunity.
  • In population studies, the major histocompatibility complex (MHC) region in 6p21 harbors genes (particularly HLA-DRB1*1501 alleles) shown to confer susceptibility to MS. However, MS is a complex genetic disease (a category of diseases thought to develop from modest genetic inheritance and complex genetic-environmental interactions), and a person having the DRB1*1501 allele(s) will not necessarily develop MS. Multiple other genes (or gene variants) must interact in concert to provide susceptibility, and an environment that helps trigger or perpetuate autoimmunity or neurodegeneration must play a role.

    Genes that instead of conferring susceptibility to MS do confer relative protection are being investigated, and clues are also emerging from within the MHC region. Recently,  the HLA-C*05 allele was suggested to confer disease protection.6

    The concordance rate for MS is only 20-35% among monozygotic twins, suggesting only a modest effect by genetic factors. The presence of other predisposing, non-Mendelian factors (ie, epigenetic modification in 1 twin) along with environmental effects play an important role.

    HLA-DRB1 is the only chromosomal locus that has been consistently associated with MS susceptibility. Some genes within the MHC region confer protection. Other gene variants (known as single nucleotide polymorphisms [SNIPS]), such as those recently found in the IL-7 and IL-2 receptor genes, are thought to play a less prominent role in disease susceptibility than MHC genes. More importantly, research on SNIPS that confer risk of more severe disease or risk of developing particular forms of MS will be of great interest to the clinicians treating this complex disease in the early stages.
  • Other molecules involved in activation of T and B cells have been implicated in MS. For instance, the co-stimulatory molecule B7-1, necessary for activation of T cells as a second signal to antigen presentation, has been found to be elevated in early MS lesions, suggesting a triggering role for inflammation within the CNS. Other factors elevated in MS brain tissues include the proinflammatory interferon gamma and the prodemyelinative tumor necrosis factor alpha molecule. In addition, interactions between molecules on the surface of B and T cells, such as CD40 and CD40 ligand, may mediate elevated levels of IL-12 (a proinflammatory cytokine) in the circulation of patients with MS.
  • The molecular mimicry hypothesis refers to the possibility that peripheral blood T cells may become activated to attack a foreign antigen, then erroneously direct their attack toward brain proteins that share similar protein epitopes.
  • Others support the hypothesis 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 both the immune and nervous systems can possibly be reactivated periodically and thus lead to acute exacerbations in MS. The Epstein Barr virus (EBV) has been found to become periodically reactivated, but a causation role in MS has been difficult to prove. Arguments supporting this view include long-term studies showing a higher association with MS in individuals with early presence of serum antibodies against specific EBV antigens, and high expression of EBV antigens within MS plaques. Arguments against demonstrating causation include the fact that MS is a highly heterogeneous disease (EBV could help trigger some cases but not others, making associations in populations difficult), and the notion that disease manifestations could precede viral reactivation (ie, the virus would be reactivated as an epiphenomenon of a dysregulated immune system and not be the actual trigger). 

More on Multiple Sclerosis

Overview: Multiple Sclerosis
Differential Diagnoses & Workup: Multiple Sclerosis
Treatment & Medication: Multiple Sclerosis
Follow-up: Multiple Sclerosis
Multimedia: Multiple Sclerosis
References
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  34. Pittock SJ, Mayr WT, McClelland RL, et al. Disability profile of MS did not change over 10 years in a population-based prevalence cohort. Neurology. Feb 24 2004;62(4):601-6. [Medline].

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Further Reading

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Keywords

multiple sclerosis, MS, multiple sclerosis treatment, multiple sclerosis symptoms, MS symptoms, MS treatment, multiple sclerosis diagnosis, myelin, inflammatory disease of central nervous system, demyelinating disease, sclerosis in plaques, CNS disease, disseminated sclerosis, focal sclerosis, insular sclerosis, elevated immunoglobulin G, interleukin-12, IL-12, B7-1, relapsing remitting MS, RRMS

secondary progressive MS, SPMS, primary progressive MS, PPMS, relapsing progressive MS, RPMS, brain atrophy, spinal cord atrophy, short-term memory problems, difficulty executing sequential tasks, visuospatial disturbances, benign MS, cognitive dysfunction, mental slowing, cognitive slowing, lack of sleep, optic nerve dysfunction, Uhthoff phenomenon, Marburg variant of MS

necrotizing myelopathy, neuromyelitis optica, Devic disease, acute disseminated encephalomyelitis, ADEM, Schilder disease, Baló concentric sclerosis, ataxia, hemiparesis, paraparesis, depression, bipolar disorder, dementia, optic neuritis, orbital pain, patchy loss of vision, cecocentral scotoma, afferent pupillary defect

facial palsies, trigeminal neuralgia, facial myokymia, nystagmus, internuclear ophthalmoplegia, painful limb syndromes, central vertigo, diplopia, dysarthria, pseudobulbar affect, social disinhibition, chronic inflammatory demyelinating polyradiculopathy, CIDP, conversion reactions, la belle indifference, urinary retention

urinary incontinence, sexual dysfunction, Kurtzke Expanded Disability Status Scale, immune dysfunction, HLA-DR2 allele, pro-demyelinative tumor necrosis factor alpha molecule, pro-inflammatory interferon gamma, proinflammatory interferon gamma

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Contributor Information and Disclosures

Author

Fernando Dangond, MD, Senior Director of Medical Affairs, Neurology, EMD Serono, Inc
Fernando Dangond, MD is a member of the following medical societies: American Academy of Neurology and American Medical Association
Disclosure: EMD Serono, Inc. Salary Employment

Medical Editor

William J Nowack, MD, Associate Professor, Epilepsy Center, Department of Neurology, University of Kansas Medical Center
William J Nowack, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Electroencephalographic Association, American Medical Informatics Association, and Biomedical Engineering Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Paraplegia Society, and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

B Mark Keegan, MD, FRCPC, Assistant Professor of Neurology, College of Medicine, Mayo Clinic; Master's Faculty, Mayo Graduate School; Consultant, Department of Neurology, Mayo Clinic, Rochester
B Mark Keegan, MD, FRCPC is a member of the following medical societies: American Academy of Neurology, American Medical Association, and Minnesota Medical Association
Disclosure: Nothing to disclose.

 
 
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