Multiple Sclerosis for APRNs Nursing CE Course

Secondary progressive MS (SPMS; see Figure 4 below) is characterized by gradual neurologic deterioration with or without relapses which develops after an initial period of the relapsing-remitting disease. Although some improvement may be noted after a relapse, there is no actual recovery period. Approximately 40% of patients with RRMS will eventually progress to SPMS. The transition for patients who progress to SPMS usually occurs 10-20 years after their initial diagnosis. There are no criteria for determining when RRMS has transitioned to SPMS; therefore, the diagnosis is often made retrospectively. There are different subcategories of SPMS, including active, not active, with progression, or without progression. Currently, the primary goal of treatment is to prevent disease progression to SPMS (Bauldoff et al., 2020; Honan, 2019; National Multiple Sclerosis Society, n.d.-h; Olek & Howard, 2022).   

Risk Factors 

Although the etiology of MS is unknown, there is speculation that environmental factors and genetic susceptibility play a role in triggering the immune response that damages the myelin sheath, which can progress to involve the oligodendrocytes, axons, and neurons. Research suggests that contracting infectious mononucleosis following exposure to the Epstein-Barr virus (EBV) may play a role in developing MS. Other suggested environmental risks include smoking, vitamin D deficiency, ultra-violet light exposure, obesity in childhood or adolescence, repeated head trauma or concussions, and treatment with anti-tumor necrosis factor-alpha (Bauldoff et al., 2020; Hinkle & Cheever, 2018; Honan, 2019; National Multiple Sclerosis Society, n.d.-d; Olek & Howard, 2022).   

Genetic predisposition increases the risk for non-Hispanic Whites. There is a greater frequency of MS in temperate regions and latitudes away from the equator. The prevalence of MS is highest in the northern US, southern Canada, Europe, New Zealand, and southern Australia. MS is less common in Asia and rarely seen in tropical or subtropical regions. One retrospective study of Americans diagnosed with MS found that non-Hispanic White Americans developed the disease earlier (31.1 years of age) than Black Americans (33.7 years). Black Americans had a shorter time between diagnosis and the initiation of treatment. Therefore, access to healthcare was not considered a contributing factor to the increase in debility seen in this population. Although diagnosed later in life, Black Americans are more likely to develop an ambulatory disability, multifocal symptoms, and disease limited to the optic nerves and spinal cord than White Americans (Hinkle & Cheever, 2018; Hoffman & Sullivan, 2017; Honan, 2019; National Multiple Sclerosis Society, n.d.-d; Olek & Howard, 2022).  

Diagnosis 

MS can be challenging to diagnose because symptoms may be intermittent and mimic other disease processes. A detailed history and physical and thorough neurological examination are essential. The neurological examination should assess for optic neuritis by checking for color desaturation or visual loss, eye movement abnormalities, including internuclear ophthalmoplegia (impaired horizontal eye movements) or nystagmus (jerking movement of the eyes either vertically or horizontally); upper motor neuron involvement causing spasticity, hyperreflexia, or a positive Babinski sign; ataxia and gait disturbance; hemisensory loss and bilateral sensory loss or paresthesia in extremities. Although there are no clinical findings unique to MS, there are findings highly indicative of MS. Unless contraindicated, patients being evaluated for MS should, at minimum, have Magnetic resonance imaging (MRI) of the brain and spine without contrast. An MRI is used to identify the presence of lesions (plaques) within the CNS. It is the gold standard diagnostic test for the clinical diagnosis of MS. (Hoffman & Sullivan, 2017; Olek & Howard, 2021). Absolute contraindications to MRI use include:   

• cardiac implantable electronic devices such as a pacemaker or implantable cardioverter-defibrillator (ICD) 

• metal intraocular foreign bodies; it is vital to ask each patient if they have ever welded without wearing proper eye protection or had a facial injury involving metal 

• implantable neurostimulator  

• cochlear implants/ear implants or hearing aids; a 1.5-tesla MRI scanner is compatible with the BAHA cochlear implant if the battery is removed before testing  

• drug infusion pumps, including those used for insulin, analgesics, or chemotherapy delivery 

• catheters that have metal components, such as a Swan-Ganz catheter  

• any foreign metal objects, including bullets, shotgun pellets, or shrapnel; it is important to ask patients to be honest about the possibility of having any foreign metal objects in their body  

• cerebral artery aneurysm clips 

• magnetic dental implants  

• tissue expander 

• artificial limbs should be removed before scanning; this does not include artificial joints following total knee arthroplasty (TKA) or total hip arthroplasty (THA)  

• piercings should be removed before scanning (Ghadimi & Sapra, 2021).  

It is essential to get a complete patient history to determine if any contraindications are present before entering the MRI room. It is also important to determine if the patient is claustrophobic, as an MRI of the brain and spine requires the patient’s upper body to enter the narrow MRI machine opening. If anxiety or claustrophobia inhibits the completion of testing, the patient may require a referral to a facility with an open MRI or premedication with an anxiolytic (Ghadimi & Sapra, 2021).  

An MRI is the most definitive test available for diagnosing a patient with MS; however, it is only one of several diagnostic tests that can be used. For patients with typical symptoms but insufficient clinical data and MRI results to confirm a diagnosis of MS, a lumbar puncture can be performed to obtain cerebrospinal fluid (CSF). The CSF is then analyzed for an increased number of T-lymphocytes (which indicate an immune response), elevated levels of IgG, and oligoclonal bands. Evoked potentials and optical coherence tomography (OCT) may also be done. Evoked potentials are used to detect subclinical changes in the function of the CNS. Evoked potentials may also help locate the anatomical region of lesions when the area cannot be clearly visualized using imaging. During the test, the patient is exposed to sensory stimuli (e.g., flashing lights) to activate areas of the brain. During this, the brain’s electrical responses to the stimuli are recorded. In patients with MS, the brain’s response to the stimuli is delayed due to demyelinated nerve fibers. OCT uses infrared light waves to image the retina at high resolution and measure the thickness of the nerve fiber layer. In 85% of patients with MS with optic neuritis, the thickness of the retinal nerve fiber layer is reduced. OCT also shows the retrograde degeneration of unmyelinated retinal nerve fiber layer axons, which occurs with demyelination of the optic nerve. These tests provide support for the diagnosis of MS. A brain CT scan may also reveal atrophy or white matter lesions (Bauldoff et al., 2020; Levin, 2021; Olek & Howard, 2021).  

The McDonald criteria can help a healthcare practitioner determine if a diagnosis of MS is indicated based on the patient’s presenting symptoms, assessment findings, and the MRI and other diagnostic testing results. One of the critical requirements for a diagnosis of MS using the McDonald criteria is evidence of damage to the CNS that is disseminated in time (DIT) and disseminated in space (DIS), which means that damage occurred to distinct areas of the CNS on separate dates. The McDonald criteria use MRI evidence extensively and suggest that an MRI is performed on all individuals for whom a diagnosis of MS is possible. The McDonald criteria are outlined as follows:  

• In a patient who experiences a typical attack: 

• The patient has experienced two or more attacks and has clinical evidence of two or more lesions OR two or more attacks with one lesion and a clear history of a previous attack involving a lesion in a different location. No additional criteria are needed to diagnose MS as both DIS and DIT have been met.  

• The patient has experienced two or more attacks and has clinical evidence of one lesion. Additional criteria to make a diagnosis of MS and demonstrate DIS include either another clinical attack that impacts a different location within the CNS or evidence of one or more additional MS-typical lesions in two or more areas of the CNS.  

• The patient has experienced one attack and has clinical evidence of two or more lesions. Additional criteria to diagnose MS and demonstrate DIT include at least one of the following criteria: another attack, CSF oligoclonal bands, or both enhancing and non-enhancing MS-typical MRI lesions or a new enhancing lesion compared to the baseline scan.  

• The patient has experienced one attack and has clinical evidence of one lesion. Additional criteria to diagnose MS must demonstrate both DIS and DIT. To demonstrate DIS, either a second attack affecting a different location within the CNS or one or more MS-typical lesions in two or more areas of the CNS must be present. To demonstrate DIT, at least one of the following criteria must be met: an additional attack; the presence of CSF oligoclonal bands; or both enhancing and non-enhancing MS-typical MRI lesions or a new enhancing lesion compared to the baseline scan.  

• In a patient that has exhibited a steady progression of symptoms since onset: 

• The patient has experienced at least one year of disease progression. Additional criteria to make a diagnosis of MS and demonstrate DIS include at least two of the following criteria: one or more MS-typical lesions; two or more spinal cord lesions; CSF oligoclonal bands (Spain & Wooliscroft, 2017). 

 Although the McDonald criteria can help determine if a diagnosis of MS is appropriate, it cannot differentiate between MS and other similar neurologic disorders. If the McDonald criteria are met, and there is no better diagnosis for the presenting symptoms, a diagnosis of MS is given to the patient. If the criteria are not entirely met, but MS is suspected based on all other findings, the patient is diagnosed as possibly having MS with necessary follow-up and reevaluation scheduled. If criteria are not met, and a different disorder better explains the patient’s symptoms, a diagnosis of MS is not given. Diagnosis is especially challenging in patients that are either younger or older than the average age of onset, have unspecific MRI results, present with atypical symptoms, or have already been diagnosed with a progressive illness. The revised version of the McDonald criteria (outlined above) reinforced the importance of MRI results, clinical presentation, and CSF analysis. (Olek & Howard, 2021).  

Signs and Symptoms 

Clinical manifestations of MS are varied and are primarily determined by the location of any current lesion or lesions. The sudden onset of a symptom may indicate a relapse. Any symptom experienced can be acute or chronic. Some patients may experience an acute symptom that they never fully recover from, leading to a chronic symptom. When managing MS symptoms, it is essential to focus on the non-visible effects and the physical manifestations of the disease, as these symptoms often have the most significant impact on the patient’s life (National Multiple Sclerosis Society n.d.-i).  

Fatigue 

Fatigue is one of the most common complaints among patients diagnosed with MS. It is often one of the most disabling symptoms, but the cause of fatigue in MS is poorly understood. Individuals with MS may describe it as the lack of physical or mental energy to complete daily activities. Fatigue is typically reported to be worse in the afternoon. Influencing factors may include depression due to the chronicity of the disease, deconditioning, and high temperatures (Hinkle & Cheever, 2018; Honan, 2019).  

Visual Disturbance 

When lesions or plaques develop in the optic nerves or their connections, the patient may experience diplopia (double vision), blurred vision, nystagmus, scotomas (blind spots), and even periods of total blindness. Visual disturbances are commonly experienced by patients diagnosed with MS. In 25% of patients with MS, optic neuritis was the initial symptom, and 50% of all patients with MS will experience optic neuritis during disease progression. Visual disturbances can significantly impact a patient’s ability to function independently or continue working (Honan, 2019; National Multiple Sclerosis Society, n.d.-i).  

Swallowing Disorders 

If the cranial nerves innervating speech and swallowing are affected, the individual may experience dysarthria (slurred speech) and dysphagia (difficulty swallowing). Therefore, it is recommended that once a diagnosis of MS is made, the primary care provider refer the patient to a speech-language pathologist (SLP) for a full workup of oropharyngeal and esophageal swallowing function to obtain a baseline against which to compare future changes. The most common MS-related swallowing disorders include xerostomia (dry mouth), decreased coordination in processing food in the mouth, delayed pharyngeal swallow, reduced laryngeal excursion, and reduced tongue base retraction. Dysphagia can lead to aspiration or a fear of choking, resulting in inadequate nutritional intake. The goal of managing dysphagia is to keep the patient on a regular texture diet for as long as possible. Once regular texture food becomes a safety concern, the SLP can perform a modified barium swallow study (MBS) to assess oral and pharyngeal swallowing function, followed by an esophagram or a fiberoptic endoscopic evaluation of swallowing (FEES) looking at esophageal function. Once swallowing function is analyzed, the SLP can recommend texture modifications (e.g., pureed diet or thickened liquids). If follow-up studies determine that the patient is aspirating despite changes to diet texture or the patient cannot maintain proper nutritional intake via the oral route, non-oral feeding options should be considered (Hinkle & Cheever, 2018; Logemann & Burnham, 2018).      

Pain 

Lesions on the sensory pathways may cause the individual to experience debilitating pain. A physical assessment finding associated with sensory pathway involvement is Lhermitte’s sign, a shock-like sensation felt down the arms and back when the individual performs cervical flexion. Disruption of these sensory axons can also lead to numbness, paresthesia, or dysesthesia. One systematic literature review found that 63% of patients with MS experience pain. The same review further delineated that 51% experienced headaches, 27% had neuropathic pain, 20% reported back pain, 17% had a positive Lhermitte’s sign, and 4% experienced trigeminal neuralgia. Individuals with different subtypes of MS report pain differently, with 69.8% of patients with PPMS, 70.3% with SPMS, and 50% of those with RRMS experiencing pain. The pain experienced by patients with MS is of greater intensity, has more impact on daily activities and quality of life, and requires higher doses of analgesic medications than the pain experienced by individuals without MS (Hinkle & Cheever, 2018; Honan, 2019; Maloni, 2016).  

Patients with MS experience different types of pain. Dysesthetic pain is continuous central neuropathic pain felt in the extremities. Dysesthetic pain is experienced by 1 in 5 patients with MS making it the most common type of constant pain. It mainly affects the legs and feet and is described as tingling or burning. This type of pain is indicative of the presence of plaque in the cervical or thoracic spinal cord. Although dysesthesia is challenging to eliminate, medications are available to decrease symptoms (Maloni, 2016). For more information, see the Nursing CE course Pain Management. 

Neurocognitive Changes  

When patients have active lesions in the cerebellum or basal ganglia, they may demonstrate ataxia (impaired coordination of movements) or tremors. Cognitive and psychosocial problems may indicate frontal or parietal lobe involvement and may present as memory impairment and loss of concentration (Hinkle & Cheever, 2018; Honan, 2019).  

Spasticity 

When the motor pathways of the spinal cord are affected, the individual may have spasticity (muscle hypertonicity) of the extremities. Spasticity is most commonly experienced in the legs. The resulting painful spasms can affect the patient’s mobility and functional independence and disrupt sleep. Clinical indications of spasticity include decreased range of motion (ROM), difficulty relaxing muscles, loss of voluntary control of muscles, pain, experiencing muscle tightness, difficulty initiating movements, and an increase in deep tendon reflexes. The Ashworth Scale is a method of grading spasticity on a 5-point numerical scale from 0-to 4, with 0 being no resistance or increase in muscle tone and 4 being limb rigidity (Hinkle & Cheever, 2018; Honan, 2019; Kushner & Brandfass, n.d.). The scale is as follows (Harb & Kishner, 2021):  

• 0: a rating of zero indicates no increase in muscle tone 

• 1: a slight increase in muscle tone manifested as a catch when performing ROM, followed by minimal resistance through the remainder (less than half) of the ROM 

• 2: a marked increase in muscle tone through most of the ROM, but the affected body part is still able to be easily moved  

• 3: a considerable increase in muscle tone, making passive movement difficult 

• 4: the affected body part is rigid during flexion or extension 

 Bladder/Bowel/Sexual Dysfunction 

Other symptoms associated with spinal cord involvement include bladder, bowel, and sexual dysfunction. When individuals experience bladder dysfunction, it typically falls into one of the following categories: (1) hyperreflexic bladder, or inability to store urine; (2) hyporeflexic bladder, or inability to empty the bladder; or (3) a mixture of both types (Hinkle & Cheever, 2018). Urodynamic studies are a set of tests used to measure the functional status of the lower urinary tract by evaluating the pressure-flow relationship between the bladder and urethra. These studies analyze the filling, storage, and voiding phases. Simple, noninvasive urodynamic tests include postvoid residual (PVR) and single-channel cystometrogram (CMG). PVR testing measures the amount of urine remaining in the bladder after complete urination using a bladder scanner. CMG assesses the sensation of bladder filling, fullness, and urgency. This is done by inserting a catheter and filling the bladder to measure capacity and storage pressures. The goal of urodynamics is to determine the correct diagnosis of lower urinary tract dysfunction. Bowel dysfunction is common in MS, with 60% of patients reporting fecal incontinence or constipation. Patients experience a higher prevalence of constipation than incontinence. Management of bowel dysfunction is guided by the cause, disease progression, or medication side effects. Bowel incontinence can be caused by sphincter dysfunction, constipation resulting in overflow or rectal overload, or diminished sensation. Bulk agents can also promote fecal consistency in those who have incontinence due to constipation. Sexual dysfunction can be due to erectile or ejaculatory dysfunction in males and orgasmic dysfunction and vaginal dryness in females (Bauldoff et al., 2020; Gill & Kim, 2019; Holland & Kennedy, n.d.).  

Mood Changes  

There are various mood changes that patients diagnosed with MS may experience, including depression, anxiety, irritability, and pseudobulbar affect (PBA). PBA affects 10% of patients with MS. It is characterized by uncontrollable laughing or crying. These issues tend to be underreported by patients to their healthcare providers and undertreated when they are reported. Untreated or undertreated depression has contributed to the high rate of suicide among patients with MS. Completing proper depression screening is essential when treating patients with MS. Mood changes can interfere with self-care, treatment adherence, performance at home or work, relationships, and quality of life (National Multiple Sclerosis Society, n.d.-i). For more information on depression, see the Nursing CE course on depression. 

Disease Severity 

The effects of MS are highly variable, and each patient’s experience is unique. The impact of MS on an individual is determined based on the severity of symptoms, frequency of relapses, rate of worsening, and residual disability. Patients with MS report that progressive disability is their most important concern. There are different scales available that healthcare professionals can use to measure disability in patients with MS. The Kurtzke Expanded Disability Status Scale (EDSS) is an updated version of the original Disability Status Scale (DSS) and is used to score clinical disability in patients with MS. The scale was updated and expanded to more accurately reflect the levels of disability seen clinically in patients diagnosed with MS. The scores range from 0 for a clinical examination within normal limits to 10 for death related to MS (Olek & Howard, 2022). The EDSS also provides eight subscale measurements known as functional system (FS) scores, which refer to the functional systems affected by MS: pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral or mental, and other (any other neurologic finding attributed to MS disease progression). Each FS is graded from 0 to 5 or 6 (depending on the system). A grade of 0 indicates a low level of disability, and 5 or 6 correlates with a high level of disability. The total EDSS score is determined based on patient ambulation ability and FS scores. EDSS scores less than 4.0 are determined based on the FS scores alone. Both ambulation ability and FS scores determine scores between 4.0 and 9.5; however, for simplicity, many clinicians gauge EDSS scores between 4.0 and 9.5 by gait alone without considering the FS scores. A score within the range of 1.0 to 4.5 indicates that full ambulatory ability is still present. In contrast, a score between 5.0 and 9.5 correlates with ambulatory impairment. The scoring of the Kurtzke EDSS is as follows:  

• 0.0: a regular neurological exam; FS scores all 0 

• 1.0: no disability with minimal signs in one FS 

• 1.5: no disability with minimal signs in more than one FS  

• 2.0: minimal disability in one FS (one FS grade 2, all others grade 0 or 1) 

• 2.5: minimal disability in two FS (two FS grade 2, all others grade 0 or 1)  

• 3.0: moderate disability in one FS (one FS grade 3, all others grade 0 or 1) or mild disability in three or four FS (three or four grade 2, all others grade 0 or 1)  

• 3.5: moderate disability in one FS (one grade 3) and one to two FS grade 2; or two FS grade 3; or five FS grade 2 

• 4.0: ambulatory without aid; relatively severe disability with one FS grade 4 or a combination of lesser grades higher than outlined in previous scores  

• 4.5: limitation of full activity or requires minimal assistance with ambulation; severe disability with one FS grade 4 or a combination of lesser grades higher than outlined in previous scores  

• 5.0: disability severe enough to impact daily living; one FS grade 5 or a combination of lesser grades higher than outlined in previous scores  

• 5.5: disability severe enough to preclude daily activities; one FS grade 5 or a combination of lesser grades higher than outlined in score 4.0 

• 6.0: intermittent or unilateral assistance needed for ambulation (e.g., cane, crutch, or brace); more than two FS grade 3 

• 6.5: constant bilateral assistance needed for ambulation; more than two FS grade 3 

• 7.0: unable to walk more than 5m despite assistive devices; restricted to a wheelchair (WC) but able to transfer independently; more than one FS grade 4 

• 7.5: restricted to WC and requires assistance to transfer; more than one FS grade 4 or higher 

• 8.0: restricted to bed or chair; still has use of arms; FS grade 4 or higher in several systems  

• 8.5: restricted to bed much of the day; decreased use of arms; FS grade 4 or higher in several systems 

• 9.0: bedbound and unable to care for self; still able to communicate and feed self; FS grade 4 or higher in several systems  

• 9.5: bedbound and unable to care for self; unable to communicate or eat/swallow; almost all FS grade 4 or higher 

• 10: death due to MS (US Department of Veterans Affairs, 2021) 

There is also a scale that allows patients to self-score called the Patient-Determined Disease Steps (PDDS) scale (Olek & Howard, 2022).  

Symptom Management  

While treatment modalities can increase periods of remission and slow the progression of MS, it is effective symptom management that improves the patient’s ability to function and experience a better quality of life. Due to this impact on a patient’s daily life, symptom management is considered an essential component of disease management (National Multiple Sclerosis Society, n.d.-i). 

Fatigue 

Medications used to manage MS-related fatigue include dextroamphetamine (Adderall), methylphenidate (Ritalin), modafinil (Provigil), and amantadine (Symmetrel). The APRN must assess the risk of abuse before prescribing dextroamphetamine (Adderall), methylphenidate (Ritalin), or modafinil (Provigil) due to their high risk of misuse. Due to the stimulant effects of these medications, it is also essential to obtain a thorough personal and family cardiac history, including sudden death or ventricular arrhythmia. Adverse effects of dextroamphetamine (Adderall) and methylphenidate (Ritalin) include mood changes, tachycardia, hypertension, and insomnia. Dextroamphetamine (Adderall) and methylphenidate (Ritalin) are contraindicated in patients with heart defects or serious heart problems. Dextroamphetamine (Adderall) is available as both immediate and extended-release tablets. The typical starting dose for the immediate release formulation is 5 mg once or twice daily. The dose may be increased by 5 mg every week until symptoms improve with a maximum daily dose of 40 mg/day. The frequency of administration can also be increased to every 4-6 hours. The typical starting dose for the extended-release formulation is 20 mg once daily. The average dose of methylphenidate (Ritalin) is 20 to 30 mg/day divided into two or three doses with a maximum daily dose of 60 mg. Modafinil (Provigil) may cause headaches, vision changes, chest pain, and irregular heart rate. It also decreases the effectiveness of oral contraceptives. The standard dose for modafinil (Provigil) is 200 mg once daily, taken in the morning. The maximum dose is 400 mg daily; however, increasing the dose over 200 mg/day may not increase effectiveness. Modafinil (Provigil) is contraindicated for use with several medications, herbs, and foods such as monoamine oxidase inhibitors (MAOIs), warfarin (Coumadin), St. John’s wart, green tea, fruit juice, and beverages that contain caffeine (due to the synergistic effect). Amantadine (Symmetrel) is an antiviral used off-label to treat MS-related fatigue. The mechanism by which it is effective for MS-related fatigue is unknown however may be due to the effect on dopamine reuptake. The typical dosage is 100mg to 200 mg/day (Levin, 2021; National Multiple Sclerosis Society, n.d.-i; Vallerand & Sanoski, 2017).   

Visual Disturbance 

High-dose corticosteroids such as prednisone (Deltasone) and methylprednisolone (SoluMedrol) can help reduce optic neuritis. Side effects of corticosteroid treatment include increased appetite, hypertension, palpitations, difficulty sleeping, and hyperglycemia. Often treatment begins with methylprednisolone (Solumedrol) 1000mg IV for 3-5 days, followed by a rapid taper (a few days) with oral prednisone (Deltasone). Oral prednisone (Deltasone) can also be used alone without starting treatment with methylprednisolone (Solumedrol). Corticosteroids are contraindicated in patients with uncontrolled hyperglycemia, glaucoma, and systemic fungal infection. Visual disturbances are challenging to treat and may become permanent; therefore, it is also important to refer patients to an ophthalmologist who specializes in decreased vision that can provide patients with adaptive equipment and educate them on environmental modifications (Goodman, 2021; Levin, 2021; National Multiple Sclerosis Society, n.d.-I; Vallerand & Sanoski, 2017).  

Swallowing Disorders  

There are three types of non-oral feeding available to ensure that a patient’s dietary requirements are met while decreasing aspiration and risk for pneumonia. The first is a nasogastric (NG) tube which can deliver tube feedings straight to the stomach. NG tubes should not be left in for longer than two weeks; therefore, this is not a long-term solution. The second option is total parenteral nutrition (TPN) or partial parenteral nutrition (PPN), administered intravenously. TPN must be administered through a central venous line, while PPN can be administered via a peripheral line. Both types of intravenous access cannot be kept indefinitely and are not appropriate as a long-term non-oral feeding option. The last non-oral feeding option involves the insertion of a feeding tube. Percutaneous endoscopic gastrostomy (PEG or G-tube) tubes are inserted through the abdominal wall directly into the stomach. In some cases, the feeding tube is inserted into the jejunum of the small intestine and is therefore called a J-tube. A PEG and J-tube are the only long-term options available for patients unable to tolerate oral intake. Although these feeding tube options decrease aspiration risk, they do not eliminate the patient’s risk (Logemann & Burnham, 2018). 

Pain 

Patients with MS often experience neuropathic pain from the damage to the nerves. Some medications FDA approved for depression and seizure disorders are used off-label to manage neuropathic pain in patients with MS. These medications include the serotonin and norepinephrine reuptake inhibitor (SNRI), duloxetine (Cymbalta), and the anticonvulsants gabapentin (Neurontin) and carbamazepine (Tegretol). All three medications can cause dizziness and drowsiness. Carbamazepine (Tegretol) can cause rare but severe effects, including toxic epidermal necrolysis, Stevens-Johnson syndrome, aplastic anemia, and agranulocytosis. The standard initial dose for carbamazepine (Tegretol) is 100-200 mg once daily. The dose may slowly increase based on the patient’s response to 1200 mg/day. The starting dose of gabapentin (Neurontin) is 300 mg once daily on day one, 300 mg twice daily on day two, then 300 mg three times daily on day three. The dose can be titrated up based on patient reports of continued pain. The maximum dose is 1800 mg/day, divided into three doses. Gabapentin (Neurontin) is contraindicated in patients with chronic kidney disease (CKD), myasthenia gravis, or decreased lung function (e.g., chronic obstructive pulmonary disease [COPD]). The recommended dosage of duloxetine (Cymbalta) is 60 mg once daily. Duloxetine (Cymbalta) should not be used in patients with chronic liver disease or severe renal impairment with a GFR < 30 mL/min (Levin, 2021; Vallerand & Sanoski, 2017). For more information on pain management, see the Nursing CE course Pain Management. 

Ataxia 

Medications that can treat ataxia include the antiepileptic gabapentin (Neurontin) and the potassium channel blocker dalfampridine (Ampyra). The side effects and contraindications of gabapentin (Neurontin) are discussed above. When used for ataxia, The standard dose of gabapentin (Neurontin) is 1200-1800 mg/day in divided doses. Dalfampridine (Ampyra) is FDA approved to improve mobility in patients with MS. The maximum dalfampridine (Ampyra) dose is 20 mg/day divided into two doses. Side effects of dalfampridine (Ampyra) include urinary tract infection (UTI), dizziness, and nausea. It is contraindicated in patients with seizures or kidney disease (Hinkle & Cheever, 2018; Levin, 2021; Vallerand & Sanoski, 2017).

Spasticity  

Treating spasticity involves the use of both pharmacological and nonpharmacological interventions. Muscle relaxants help depress the CNS to reduce pain and inhibit reflexes at the spinal level, reducing muscle spasm frequency. Baclofen (Lioresal) is FDA approved to treat spasticity in MS. The recommended dose is initially 5 mg three times daily, with dosage increases by 5 mg every three days until spasticity improves. The maximum amount is 80 mg/day, divided into four doses. Adverse effects include drowsiness, dizziness, and weakness. Abrupt discontinuation of baclofen (Lioresal) may result in seizures or hallucinations. Baclofen (Lioresal) is contraindicated for patients with schizophrenia, psychotic disorder, kidney failure, seizures, and a history of stroke. If spasticity is severe and not sufficiently controlled with oral medications, placement of an intrathecal baclofen (Lioresal) pump may be indicated. As an adjunct to oral medications, botulinum toxin (Botox) injections directly into the specific muscle and phenol nerve blocks can be effective, especially in difficult to manage cases. Physical therapy for spasticity should be initiated as soon as possible following the initial onset of symptoms. The focus of physical therapy should be on stretching and ROM, strengthening, and improving balance (Bauldoff et al., 2020; Hoffman & Sullivan, 2017; Honan, 2019; Kushner & Brandfass, n.d.; Levin, 2021).  

Bladder/Bowel/Sexual Dysfunction 

Anticholinergics may be prescribed for bladder spasticity. Overactive bladder can be managed with darifenacin (Enablex), a selective muscarinic antagonist that works by relaxing the smooth muscles of the bladder. The recommended starting dose is 7.5 mg/day. Adverse effects include constipation, nausea, and UTI. Tamsulosin (Flomax) also relaxes the bladder muscles to improve urine flow and bladder emptying. Tamsulosin (Flomax) is not approved for use in females but has been used off-label in females. The standard dose of tamsulosin (Flomax) is 0.4 mg/day taken at bedtime. Adverse effects include dizziness, diarrhea, and insomnia. In addition, ascorbic acid (Vitamin C) may be recommended to acidify the urine, making bacterial growth less likely, thus decreasing UTI risk (Goodman, 2021; Hinkle & Cheever, 2018; Vallerand & Sanoski, 2017).  

There are many interventions available to help return bowel function to baseline. Increasing fluid and dietary fiber intake can increase bowel regularity. Any bladder dysfunction experienced by the patient should be addressed before recommending increased fluid intake. Increasing dietary fiber to 25 g/day for females and 38 g/day for males is essential. If the patient is unable to get adequate fiber through nutritional modifications, bulk supplements such as psyllium (Metamucil), wheat dextrin (Benefiber), or methylcellulose (Citrucel) can be used to supplement dietary intake. Patients using these bulk supplements must be able to consume 6-8 glasses of fluid per day to prevent potential impaction. Liquid sugar concentrates, such as sorbitol (Arlex) and lactulose (Enulose), soften the stool, have very few side effects, and are good options for long-term use. Other oral interventions that can help prevent or treat constipation include docusate (Colace), magnesium hydroxide (Milk of magnesia), and polyethylene glycol (MiraLAX). Rectal interventions can consist of suppositories, such as glycerin (Glycerol) or bisacodyl (Dulcolax), or the use of enemas, such as fleets or mineral oil. Anticholinergic drugs can also be used to treat incontinence caused by hyperactive bowel. Baclofen (Lioresal) and tizanidine (Zanaflex) used to help minimize other MS symptoms can contribute to fecal incontinence and may require a dosage change to reduce side effects (Holland & Kennedy, n.d.).  

Males experiencing erectile dysfunction may benefit from oral medications such as sildenafil citrate (Viagra), tadalafil (Cialis), or vardenafil hydrochloride (Levitra). Other options to obtain an erection include injectable medications, such as papaverine (Pavabid) or alprostadil (Caverject), and mechanical devices. Females experiencing vaginal dryness may benefit from using water-soluble lubricants (Bauldoff et al., 2020). For more information on sexual dysfunction, see the Nursing CE course on sexual dysfunction. 

Mood Changes  

Patients experiencing PBA now have an FDA-approved treatment option, dextromethorphan HBr and quinidine sulfate (Nuedexta). The most common side effects include diarrhea, dizziness, vomiting, weakness, and edema. Dextromethorphan HBr and quinidine sulfate (Nuedexta) are contraindicated in patients taking MAOIs and paroxetine (Paxil), diagnosed with myasthenia gravis, prolonged QT interval, and complete atrioventricular (AV) block without a pacemaker. The starting dose of dextromethorphan HBr and quinidine sulfate (Nuedexta) is 20/10 mg once daily for seven days, then 20/10 mg twice daily as a maintenance dose. For patients suffering from depression and anxiety, cognitive behavior therapy and commitment therapy are recommended as treatment options (National Multiple Sclerosis Society, n.d.-I; Vallerand & Sanoski, 2017). For more information on depression, see the Nursing CE course on depression. 

Treatment  

Glucocorticoids 

During an exacerbation, the goal is to decrease inflammation and induce remission. A high-dose glucocorticoid, such as intravenous methylprednisolone (SoluMedrol), intravenous dexamethasone (Decadron), or oral prednisone (Deltasone) are used to exert anti-inflammatory effects on T-cells and cytokines. The most common dosage regimen is methylprednisolone (Solumedrol) 500-1,000 mg administered intravenously over a 3 to 5-day period, followed by a tapering dose with oral prednisone for 1-3 weeks. The healthcare provider (HCP) should actively monitor for adverse effects, including hyperglycemia, hypokalemia, hypertension, palpitations, lower extremity edema, mental disturbances (e.g., manic psychosis), avascular necrosis of bone, and gastrointestinal (GI) perforation. In treating PPMS or SPMS, patients receive monthly intravenous (IV) boluses of 1000 mg of methylprednisolone (SoluMedrol). This treatment combined with beta interferons has not been shown beneficial in the treatment of RRMS (Goodman, 2021; Honan, 2019; Olek & Mowry, 2022; Vallerand & Sanoski, 2017).  

Monoclonal Antibodies  

The use of monoclonal antibodies has decreased relapse rates in patients with RRMS. Examples of monoclonal antibodies used in RRMS include natalizumab (Tysabri), ocrelizumab (Ocrevus), ofatumumab (Kesimpta), and alemtuzumab (Lemtrada). Natalizumab (Tysabri) is designed to hinder the movement of damaging immune cells from the bloodstream across the blood-brain barrier into the brain and spinal cord. The standard dose is 300 mg, administered as a one-hour infusion every four weeks. Natalizumab (Tysabri) has shown to be more effective than many other MS disease-modifying treatments, particularly oral and injectable therapies. In clinical trials, natalizumab reduced the relapse rate by 54-68% compared to the 33% seen with interferon beta-1a (Avonex/Rebif) or glatiramer acetate (Copaxone) treatment. Due to the severity of the side effects, the risk/benefit ratio requires consideration by the APRN before prescribing. Although rare, progressive multifocal leukoencephalopathy (PML), an opportunistic infection, caused by the human polyomavirus 2 (previously the John Cunningham [JC]) virus, can occur. PML is characterized by the onset of dementia, progressive weakness, vision changes, coma, and may lead to death. Natalizumab (Tysabri) is contraindicated in patients with a history of PML (Goodman, 2021; National Multiple Sclerosis Society, n.d.-b; Olek & Mowry, 2022; Smelkowska et al., 2018; Wilson et al., 2017).  

Ocrelizumab (Ocrevus) is used to treat relapsing or primary progressing forms of MS. The standard dose for MS is 300mg given over 2.5 hours via infusion for two doses two weeks apart. Following the initial two doses, subsequent infusions of 600 mg over 3.5 hours via infusion will be needed every 6 months. Adverse effects include dizziness, hypotension, tachycardia, respiratory infection, edema, and infusion site reactions. If infusion site reactions do occur, the infusion may be slowed down. Before the next infusion, premedication with methylprednisolone (SoluMedrol), diphenhydramine (Benadryl), and acetaminophen (Tylenol) may prevent infusion side effects (Goodman, 2021; Levin, 2021; Vallerand & Sanoski, 2017).  

Ofatumumab (Kesimpta) is used to treat relapsing forms of MS. Ofatumumab (Kesimpta) should be administered subcutaneously only. Initial dosing is 20 mg administered once weekly for three weeks. Subsequent dosing is 20 mg administered monthly beginning week 4. Ofatumumab (Kesimpta) is contraindicated in patients with a history of hepatitis B infection, history of PML, received a live or live-attenuated vaccine within four weeks of starting treatment. Infusion reactions are common and can occur up to 24-hours following injection. The most common side effects include upper respiratory infection and headache. Laboratory testing must be completed to monitor immunoglobulin levels before starting ofatumumab (Kesimpta), during treatment, and after completion of treatment. If a severe opportunistic infection occurs, the medication should be discontinued (Goodman, 2021; Levin, 2021; Vallerand & Sanoski, 2017).  

Alemtuzumab (Lemtrada) is effective in treating relapsing patterns of MS. Alemtuzumab (Lemtrada) is administered in different courses. Dosing for the first treatment course is 12 mg/day administered on five consecutive days. The second treatment course occurs 12 months after the first treatment course. Dosing for the second treatment course is 12 mg/day administered on three consecutive days. Subsequent treatment courses follow the dosing of the second treatment course and must occur 12 months apart. Alemtuzumab (Lemtrada) increases the risk of severe and sometimes deadly autoimmune disorders such as immune thrombocytopenic purpura (ITP), anti-glomerular basement membrane disease, and certain cancers, including thyroid cancer, melanoma, and lymphoma. This medication should only be prescribed when two or more other drugs have been ineffective. Severe and life-threatening infusion reactions can occur; therefore, patients must be closely monitored during infusion. Due to these risks, alemtuzumab (Lemtrada) is only available through a restricted program known as the Lemtrada Risk Evaluation and Mitigation Strategy (REMS) Program. Alemtuzumab (Lemtrada) is contraindicated in patients with kidney disease, clotting disorders, recent infection, or who received a live vaccine within six weeks of administration (Goodman, 2021; Levin, 2021; Vallerand & Sanoski, 2017).  

Immunomodulators 

Disease-modifying Therapy  

Disease-modifying therapy (DMT) aims to reduce, not eliminate, the frequency of relapses, the length of the relapse, and the number and size of the lesions (plaques) visible on the MRI. Following diagnosis, these medications should be started as early as possible. These medications are not prescribed to improve symptoms. The APRN must monitor the patient for medication regimen adherence, adverse effects, and effectiveness (American Academy of Neurology [AAN], 2018; Honan, 2019).  

Interferon beta-1a is available in an intramuscular form under the brand name Avonex. The standard dose of interferon beta-1a (Avonex) is 30 mcg, administered once weekly. Interferon beta-1a is available in a subcutaneous form under the brand name Rebif. The standard dose of interferon beta-1a (Rebif) is 22 mcg or 44 mcg, administered three times per week. The primary mechanism of action of interferons is reducing inflammation by limiting the movement of inflammatory cells to the CNS through the blood-brain barrier. A common side effect of all interferon beta medications is flu-like symptoms such as fevers, chills, and body aches, which can be reduced by concurrent administration of acetaminophen (Tylenol) or ibuprofen (Motrin) and administering the medication at bedtime. Additional side effects include leukopenia, thrombocytopenia, anemia, liver dysfunction, fetal abnormalities, and depression. Patients should have routine laboratory tests, including complete blood counts with differential and liver function studies. Liver damage is a common adverse effect of interferon beta-1a (Rebif). If liver enzymes increase or leukopenia is identified interferon beta-1a (Rebif) dose should be decreased by 20%-50%. The individual and family should be advised to notify the HCP if thoughts of suicide are experienced or expressed to others (Goodman, 2021; Honan, 2019; Smelkowska et al., 2018; Vallerand & Sanoski, 2017).  

Glatiramer acetate (Copaxone) is available as an injectable. The standard dose is 20 mg/day or 40 mg once weekly, administered by subcutaneous injection. It may take up to six months to demonstrate effectiveness. It is believed to affect T-cell activation and proliferation. Adverse reactions include swelling, inflammation, and redness at the injection site. Patients should have routine laboratory tests, including liver function studies, due to the risk of liver failure. If signs or symptoms of liver failure are reported, discontinuation of the therapy is recommended. Glatiramer acetate (Copaxone) may also affect immune function and increase the patient’s risk of contracting an infection (Honan, 2019; Levin, 2021; Smelkowska et al., 2018; Vallerand & Sanoski, 2017).  

Fingolimod (Gilenya) is a daily oral medication that helps trap immune cells in the lymph nodes resulting in a decrease in the frequency of relapses and a delay in disability. Standard dosing is 0.5 mg once daily for patients weighing over 40 kg and 0.25 mg daily for patients weighing less than 40 kg. Monitoring is required for at least 6 hours after the first dose and periodically during therapy due to the risk of bradycardia and hypotension. Side effects include headache, upper respiratory infection, flu-like symptoms, and increased liver enzymes. Patients should have routine laboratory tests, including liver function studies, due to the risk of liver failure. Fingolimod (Gilenya) is contraindicated for patients that have had a heart attack, stroke, or unstable angina in the last six months. It is also contraindicated in patients diagnosed with heart failure or arrhythmia (Bauldoff et al., 2020; Levin, 2021; Vallerand & Sanoski, 2017).   

Antineoplastics  

Mitoxantrone (Novantrone) can help reduce the frequency of relapses in individuals with SPMS or worsening RRMS. The recommended dose is 12 mg/m2 of body surface area given via intravenous infusion over 5 to 15 minutes every three months. The maximum lifetime dose should not exceed 72 mg/m2. Cardiac toxicity is a severe adverse effect and may not occur until years after the last dose. Therefore, close monitoring is required to evaluate the patient for decreased left ventricular function; an echocardiogram should be performed before each dose. This medication should not be used in patients with anemia, thrombocytopenia, fungal or bacterial infection, or decreased bone marrow function. Due to the risks of cardiac toxicity, ovarian failure, male infertility, and promyelocytic leukemia, coupled with the limited evidence of effectiveness, treatment with mitoxantrone should only be initiated if the benefits greatly outweigh the risks (Hinkle & Cheever, 2018; Levin, 2021; Olek & Mowry, 2022; Vallerand & Sanoski, 2017; Wilson et al., 2017).  

Nonpharmacological Management  

Complementary and alternative medicine (CAM) includes a variety of interventions that can help patients living with MS. When an intervention is used with traditional treatment, it is considered complementary, and when used in place of conventional medicine, it is considered alternative (National Multiple Sclerosis Society, n.d.-a). There are a variety of different CAM approaches used by patients with MS.  

• Food and diet: various diets are promoted as MS cures; however, no diet has been found effective in modifying the course of MS following diagnosis. Healthcare providers recommend that patients with MS follow the same high-fiber, low-fat diet recommended for all adults. 

• Exercise: patients with MS can experience several benefits from regular aerobic exercise; some report reduced fatigue, improved bowel and bladder function, increased strength, and mood improvement. 

• Stress management: increased stress can have health implications for all patients, including those diagnosed with MS; individuals have used meditation and Tai chi to decrease stress levels. 

• Acupuncture: this therapy is becoming more popular in Western medicine; some studies suggest that acupuncture can decrease pain and improve gait (National Multiple Sclerosis Society, n.d.-a).  

The concern with CAM is that most interventions are not FDA-approved. Although some researchers have begun testing the effectiveness of interventions such as vitamin D supplementation, exercise, acupuncture, and cooling techniques through clinical trials, there is still no definitive data demonstrating their effectiveness (National Multiple Sclerosis Society, n.d.-a). 

Other healthcare disciplines should also be involved in the care of patients with MS. A physical therapy consultation can help the client with exercises to improve muscle function and determine the need for assistive devices to maintain safety through fall prevention. An occupational therapy consultation will help determine if the client needs assistive devices for fine motor skills to promote independence and suggest measures to promote energy conservation (Hinkle & Cheever, 2018). Consultation with an SLP is needed if the individual is experiencing speech or swallowing problems (Honan, 2019).  

Future Research and Trends 

Researchers continue to discover new treatments and diagnostic tools related to MS. Within the last two years, three new medications have been FDA approved for the treatment of relapsing forms of MS: ozanimod (Zeposia), monomethyl fumarate (Bafiertam), and ofatumumab (Kesimpta). In addition, researchers are currently trying to understand how gut bacteria may influence the severity of MS, which may uncover approaches to stopping MS. They are also testing different methods to protect the nerves from demyelination and repair the myelin that has been damaged. Large clinical trials are currently being conducted on new approaches to treating progressive MS (National Multiple Sclerosis Society, n.d.-g).  

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