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      Anonymous
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      Multiple Sclerosis Overview Presentation DDx Workup Treatment Medication Updated: Apr 7, 2014
      Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

      Practice Essentials
      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.

      According to the the largest study on switching from natalizumab to fingolimod to date, a washout period shorter than 3 months was associated with a significantly lower risk of relapse. In the study of 333 MS patients switching from natalizumab to fingolimod, researchers found that a shorter washout period was also associated with significantly less disease activity during the washout period. Patients who discontinued natalizumab treatment because of poor tolerance or lack of efficacy were at significantly higher risk of relapse.[1, 2]

      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
      Optic neuritis
      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)
      Heat intolerance
      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.

      Diagnosis
      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
      Classification

      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[3, 4, 5, 6] :

      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.

      Management
      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[7]
      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)[8]
      Interferon beta-1b (Betaseron, Extavia)[9]
      Glatiramer acetate (Copaxone)[10]
      Natalizumab (Tysabri)[11, 12]
      Mitoxantrone[13]
      Fingolimod (Gilenya)[14]
      Teriflunomide (Aubagio)[15]
      Dimethyl fumarate (Tecfidera)[16, 17, 18, 19]
      A single-use autoinjector is also available for self-injection of interferon beta-1a (Rebif) in patients with relapsing forms of MS.[20]

      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
      See Treatment and Medication for more detail.

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