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Relapse Management

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Overview

Relapse Management

A relapse is considered any new or acutely worsening neurological symptoms with objective evidence that (Berkovich, 2016; Thrower, 2009):
  • Is consistent with inflammation and demyelination
  • Lasts for more than 24 hours
  • Is separated by at least 30 days from the onset of the last relapse
  • Is not related to an infection, fever, or other stresses
  • Has no other explanation
Determining whether a person is having a true relapse can be challenging. Pseudorelapses (also called pseudoexacerbations) can be caused by fatigue, overexertion, fever, infection (UTI) and exposure to heat and humidity. And fluctuations in symptoms can occur for reasons other than a relapse.

An infection is associated with an increased relapse risk, typically 3-6 weeks after the infection has resolved. Evidence also points to an association between known MS risk-associated single nucleotide polymorphisms (SNPs) and MS relapses (Lin et al., 2013).

Medication options

IV Methylprednisolone (IVMP)

The pivotal Optic Neuritis Treatment Trial (ONTT) demonstrated the efficacy of IVMP 1 g/day for 3 days in acute optic neuritis, thus laying the foundation for the treatment of MS exacerbations (Beck et al., 1992). IVMP for 3 days was also shown to significantly delay the development of MS within the first two years.

High Dose Oral Prednisone

A 1250 mg dose of oral prednisone has a bioavailability equal to 1 g IVMP (Morrow et al, 2004). Several studies have found high dose intravenous and high dose oral glucorticosteroids to be equally efficacous in accelarting recovery from relapses (Liu et al., 2017).  However, the lower cost of oral prednisone may be a consideration.

Intramuscular adrenocorticotrophic hormone (ACTH)

ACTH is FDA-approved and available for the treatment of exacerbations of MS in adults. Although ACTH has been shown to be as effective as IVMP in managing relapses (Kalinsik 2015, Arnason et al., 2013; Thompson et al., 1989; Milanese et al., 1989; Barnes et al., 1985), it is prescribed much less often because of its high cost.

Plasmapheresis

In 2011, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) recommended plasmapheresis as a second-line treatment for steroid-resistant exacerbations in relapsing forms of MS (Cortese et al., 2011).

Intravenous Immunoglobulin (IVIG)

IVIG may be considered for relapses during pregnancy (during which time steroids should be avoided if possible), and it may reduce the risk of post partum relapses (Hellwig et al., 2009; Achiron et al., 2004). IVIG is sometimes used to treat relapses that don’t respond to corticosteroids (Thrower, 2009), although the supportive evidence is limited.

During pregnancy, relapses severe enough to warrant treatment can be safely managed with a short course of corticosteroids after the first trimester. Methylprednisolone is the preferred drug because it is metabolized before crossing the placenta (Ferrero et al., 2004). IVIG is safe for use during pregnancy and may provide some benefit (Ferrero et al., 2004, Winkelmann et al., 2018).
 

Role of rehabilitation

The rehabilitation team has a key role to play in helping people regain and/or optimize function following a relapse. Published data suggest that IVMP plus rehabilitation by a multidisciplinary team is more effective than IVMP alone (Craig et al., 2003; Nedeljkovic et al., 2016) in relapse management. Rehabilitation is also useful for individuals with relapsing-remitting MS who have accumulated moderate to severe disability as a result of incomplete recovery from relapses (Liu et al., 2003). A 2017 review (Khan and Amatya, 2017) identified evidence supporting a variety of rehabilitation strategies in MS. 

Rehabilitation strategies targeted to the needs of the individual might include, among others:

  • Physical therapy (an exercise program to enhance strength balance/stability, gait, and endurance, as well as assessment for and use of mobility aids)
  • Occupational therapy (energy conservation; use of adaptive equipment in the home and work place; cognitive strategies)
  • Speech/language pathology (assessment and management of dysarthria, dysphonia, and dysphagia)
  • Nursing (bladder and bowel management)

These multidisciplinary strategies work to enhance function and promote safety and quality of life throughout the disease course.

Emotional support

Patients and families experience acute relapses of MS as crises that disrupt the status quo. These events elicit strong emotional reactions, including grief, anxiety, anger, and guilt, which need to be acknowledged and understood in order to ensure effective clinician-patient communication about the disease and its management (Kalb, 2007).

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