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December 21, 2023 at 1:45 pm #2966
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InactiveMultiple 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 HealthPractice 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
ClassificationMS 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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