08.11.2020

Symptom Management in Multiple Sclerosis

Our August Palliative Pearls Case Study highlights a patient who has a primary diagnosis of secondary progressive multiple sclerosis (SPMS). In this case, we will explore how MC’s multiple sclerosis may be contributing to her feeling fatigued and hopeless as well as consider possible treatments for urine incontinence. We will further outline what can be done to manage both depression and fatigue to help MC feel better, we will also address how to minimize her incontinence occurrences. We encourage you to download this month’s case study to share with your colleagues or continue reading below.

PATIENT CASE

MC is a 62 y/o female with a primary diagnosis of secondary progressive multiple sclerosis (SPMS) and was admitted to hospice services 1 month ago. She has a comorbid of essential hypertension and no known drug allergies. MC resides at home with her husband.

Current medications:

  • Prednisone 20mg; 1 tablet by mouth daily for pain
  • Morphine extended-release 60mg; 1 tablet by mouth every 12 hours for pain
  • Gabapentin (Neurontin®) 800mg; 1 tablet by mouth every 12 hours for nerve pain
  • Lorazepam (Ativan®) 1mg; 1 tablet by mouth twice daily for anxiety
  • Baclofen 10mg; 1 tablet by mouth 3 times daily for spasticity
  • Polyethylene glycol (MiraLAX®); Dissolve 17 grams in 8 ounces of water and drink daily to prevent constipation
  • Dronabinol (Marinol®) 5mg; 1 capsule by mouth 3 times daily to improve appetite
  • Saliva substitute; Swish and spit 1 teaspoonful in mouth as directed, as needed for dry mouth

MC discontinued ocrelizumab (Ocrevus®) therapy prior to hospice admission and was initiated on prednisone at that time. MC gets into her wheelchair with assistance daily but is spending more and more time in bed. She has been feeling down over the past two weeks despite spending time with her children and grandchildren. During this time, she has frequently commented on how fatigued and hopeless she feels. In addition, she is now incontinent of urine. MC’s pain is at goal on her current regimen and her bowels are regular. MC’s preference to forego interventions such as resuscitation, tracheostomy and enteral feeding tubes is reaffirmed.

OVERVIEW

Multiple sclerosis (MS) is an immune-mediated, demyelinating disorder affecting the myelin of the nerves in the central nervous system (CNS) (brain and spinal cord).1 Myelin is a sheath, or an insulating layer, formed around nerves to allow the quick and efficient transmission of nerve impulses along the nerve cells. Inflammation in MS destroys the myelin in variable degrees, producing lesions, or plaques, that effectively disrupt connections to the brain and spinal cord, causing significant physical disability.1-3 MS is characterized by the following conditions and symptoms that may vary temporally and in severity:3-5

  • Limited Mobility – Assistance is needed with activities of daily living. Most patients will be restricted to a bed or chair. Patients may experience skin breakdown, muscle atrophy, and decubitus ulcers as a result.
  • Difficulty Communicating – Manifests as trouble forming words and verbalizing needs.
  • Pain/Discomfort – Sources include muscle spasms, nerve pain, and pressure sores.
  • Fatigue – One of the most common symptoms and can result from lack of sleep, increased energy requirements, and/or depression.
  • Depression – Mood swings and depression are common as brain function and mental status changes. Patients may also express suicidal ideation.
  • Bladder/Bowel Problems – Patients may become incontinent of the bladder, bowel, or both. These issues can be particularly taxing on caregivers.
  • Dysphasia – Trouble swallowing progresses as muscles weaken. Patients may also have difficulty holding utensils or may forget to eat or how to swallow.

In most cases, MS progresses slowly over months or years. Life expectancy has increased in recent years due to new treatments to prevent attacks, improved healthcare and lifestyle change recommendations.3 Persons with MS should expect a life expectancy of 7 to 14 years less than the general population – time and symptom burden are dependent on other medical conditions that may complicate treatment and the type of MS diagnosed.1,5

TYPES

  • Clinically Isolated Syndrome (CIS) – The first episode of symptoms, lasting at least 24 hours – typical of MS but does not meet criteria for a diagnosis of MS yet; people with CIS may or may not develop MS.
  • Relapsing-Remitting MS (RRMS) – Most common; symptoms come and go with extended periods between attacks and may disappear during this time. Condition does not progress (worsen) at this stage.
  • Secondary Progressive MS (SPMS) – Symptoms come and go however begin to steadily get worse. Over time, a person with this type will stop having remissions (periods of no symptoms).
  • Primary Progressive MS (PPMS) – Least common; gradual worsening of symptoms that begins at the time of diagnosis. Relapses and remissions are less common.1,2,5

DISEASE-MODIFYING THERAPY

Disease-modifying therapy is indicated for RRMS but may not be as effective in treating SPMS or PPMS. The goal of immunomodulatory or immunosuppressive therapies is to decrease relapse rates, reduce relapse severity, and decrease accumulation of lesions in the CNS. Most patients will continue preventative therapy for life or until their goals of care dictate otherwise.1 These therapies include:1,3,6

Immunomodulators:

  • Interferon beta-1b (Betaseron®, Extavia®)
  • Interferon beta-1a (Avonex®, Rebif®)
  • Peginterferon beta-1a (Plegridy®)
  • Alemtuzumab (Lemtrada®)
  • Natalizumab (Tysabri®)
  • Ocrelizumab (Ocrevus®)
  • Glatiramer acetate (Copaxone®, Glatopa®)
  • Teriflunomide (Aubagio®)
  • Dimethyl fumarate (Tecfidera®)
  • Monomethyl fumarate (Bafiertam®)

Immunosuppressives:

  • Mitoxantrone
  • Siponimod (Mayzent®)
  • Fingolimod (Gilenya®)
  • Ozanimod (Zeposia®)

ACUTE EXACERBATIONS (FLARES OR ATTACKS)

An “attack” of MS is characterized by one or more of these symptoms:

  • Feels like numbness, tingling, “pins and needles”
  • Muscle weakness or spasms (person may drop things or fall)
  • Vision issues or eye pain
  • Dizzy or off-balanced (may cause falls)
  • Problems with bladder (urine) or bowel (stool) control
  • Heat sensitivity (worsens symptoms)
  • Trouble thinking clearly1,2

Most flares of MS will have minimal impact on a patient’s function thus treatment is not needed. If a patient does develop symptoms that impair function, such as loss of vision or motor symptoms, or balance/coordination problems, treatment with corticosteroids is indicated. Courses of oral or injectable dexamethasone, methylprednisolone or prednisone are common.1,3

MANAGEMENT BY SYMPTOM:

Pain/Discomfort:1,3

  • Physiotherapy
  • Therapies for nerve pain – Tricyclic antidepressants (e.g., desipramine), anticonvulsants (e.g., gabapentin (Neurontin®), pregabalin (Lyrica®), carbamazepine (Tegretol®))
  • Therapies for spasticity – Oral baclofen (Lioresal®), tizanidine (Zanaflex®), or dantrolene; intrathecal baclofen for refractory cases
  • Other adjunctive therapies – NSAIDs, acetaminophen, opioids

Difficulty Communicating:

  • Advance care planning early

Fatigue:1,3,4,7

  • Stress management, relaxation training, and/or psychotherapy
  • Keeping the room at a cooler temperature may prevent overheating
  • Stimulants – Modafinil (Provigil®), dextroamphetamine (Adderall®), methylphenidate (Ritalin®)
  • Antidepressant therapy for those with underlying depression

Depression:1,4,8

  • Psychotherapy used alone or with antidepressants
  • Physical activity – even small amounts of activity can help with depression symptoms (may become more difficult as MS progresses)
  • Antidepressant therapy – Data are limited on the best antidepressant for patients with MS.1 SSRIs (e.g., citalopram (Celexa®), fluoxetine (Prozac®), paroxetine (Paxil®), sertraline (Zoloft®)) are often selected due to comparatively less side effects and potential drug interactions.
  • Antidepressant therapy for those with underlying pain – SNRIs (e.g., duloxetine (Cymbalta®)) or tricyclic antidepressants (e.g., desipramine)

Bladder Dysfunction – Urinary Incontinence:1,3,4,9

  • Avoidance of foods or drinks with diuretic properties
  • Restriction of fluids, particularly a few hours before bed
  • Scheduled toileting (i.e., timed voiding)
  • Intermittent catheterization or in-dwelling catheter placement
  • Anticholinergic therapy – When feasible and tolerable, initiate long-acting or once-daily therapies (e.g., tolterodine (Detrol® LA), oxybutynin (Ditropan® XL, Oxytrol® transdermal), mirabegron (Myrbetriq®), solifenacin (Vesicare®)); alternative short-acting agents include tolterodine (Detrol®) and oxybutynin (Ditropan®); for refractory cases, consider botulinum toxin injections

Bowel Dysfunction:3,4,10

  • Drinking an adequate amount of fluids, when tolerated
  • Including fiber in the diet, when feasible
  • Scheduled toileting (i.e., timed voiding)
  • Constipation – stool softening with docusate (Colace®) and/or laxative therapy with psyllium (Metamucil®) or methylcellulose (Citrucel®)
  • Diarrhea – diphenoxylate and atropine (Lomotil®)

Dysphagia:4,11

  • Advance care planning early
  • Postural change – Changing a patient’s body position can redirect food for better control and coordination of swallowing
  • Patient/caregiver education – Increasing awareness and assessment of swallowing function can relieve anxiety
  • Diet texture modification – Making solid foods softer or liquids thicker can help decrease the effort required for a patient to swallow. See Palliative Pearls “Dysphagia and Thickened Liquids”.
  • Resistance exercises – Can improve the coordination and muscles involved in swallowing

ASSESSMENT AND RECOMMENDATIONS

MC is exhibiting symptoms of depression by feeling down, fatigued, and hopeless consistently over a 2-week period. Depression is experienced by almost two-thirds of patients with MS and risk of suicide is two times higher than in the general population.1 It’s important to recognize these symptoms early and to promptly manage. In addition to psychotherapy, an SSRI such as sertraline (Zoloft®) can be initiated to manage both depression and fatigue. Since MC’s pain is currently managed with morphine, gabapentin and baclofen, an SNRI, such as duloxetine (Cymbalta®) would not be necessary. Although the full effect of sertraline may not be experienced for 4 to 6 weeks, improved mood and increased energy are benefits that begin within the first week of therapy.

Bladder dysfunction is reported in up to 75% of patients with MS.1 Nonpharmacologic management includes restriction of fluids, particularly a few hours before bed, and scheduled toileting (i.e., timed voiding). MC experiences xerostomia (dry mouth) as evidenced by saliva substitute therapy, therefore beginning anticholinergic therapy, which may worsen this symptom, is reserved for when non-drug therapies fail. When anticholinergic therapy is necessary, MC’s swallowing capabilities should be assessed before choosing an appropriate agent. Oxytrol® transdermal patch may offer ease of administration, being topical and just twice weekly, and has a lower incidence of xerostomia (7.5-12.1%) compared to oxybutynin immediate-release tablets (71.4%). Extended-release oxybutynin has a similar incidence of xerostomia (4.1-9.6%).6

REFERENCES:

  1. Blais CM, et al. Essential Practices in Hospice and Palliative Medicine. UNIPAC 9: HIV, Dementia, and Neurological Conditions, 5th ed. Shega JW, Paniagua MA, eds. Chicago, IL: AAHPM, 2017.
  2. Patient education: Multiple sclerosis in adults (The Basics) In: UpToDate. Accessed August 5, 2020.
  3. Luzzio C, et al. Multiple Sclerosis. In: Medscape Drugs & Diseases – Neurology. Chawla J, Talavera F, eds. Updated April 30, 2020. https://emedicine.medscape.com/article/1146199-overview#a1
  4. National Multiple Sclerosis Society. Medications. Accessed July 20, 2020. Available from: https://www.nationalmssociety.org/Treating-MS/Medications
  5. National Multiple Sclerosis Society. Definition of MS. Accessed August 5, 2020. Available from: https://www.nationalmssociety.org/What-is-MS/Definition-of-MS
  6. Clinical Pharmacology [database online]. Tampa, FL: Elsevier/Gold Standard, Inc.; 2020. Accessed August 5, 2020.
  7. National Multiple Sclerosis Society. Fatigue. Accessed July 20, 2020. Available from: https://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms/Fatigue
  8. National Multiple Sclerosis Society. Depression. Accessed July 20, 2020. Available from: https://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms/Depression
  9. National Multiple Sclerosis Society. Bladder Problems. Accessed July 20, 2020. Available from: https://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms/Bladder-Dysfunction
  10. Holland NJ. Bowel management in multiple sclerosis. National Multiple Sclerosis Society. 2018. Accessed July 20, 2020. https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Clinical_Bulletin_Bowel-Management-in-MS.pdf
  11. Logemann JA, Burnham A. A resource for healthcare professionals: Swallowing disorders and their management in patients with MS. National Multiple Sclerosis Society. 2018. Accessed July 20, 2020. Available from: https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Clinical-Bulletin-Swallowing-Disorders-and-Their-Management.pdf

 

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