There is currently no cure for multiple sclerosis (MS), but effective strategies are available to manage the disease, treat acute exacerbations, and improve overall function. Treatment management has two main objectives1: to relieve symptoms acutely and to prevent further disease progression.
Most disease-modifying agents for MS have been approved for use only in relapsing-remitting forms of MS2. Treating the progressive forms of MS is more difficult than treating the relapsing forms. Specific drugs and non-pharmacologic interventions are available to treat common acute symptoms such as fatigue, spasticity, depression, bladder dysfunction, and optic neuritis.
Patient lifestyle, disease stage, tolerance, and anticipated adverse effects should be considered when choosing appropriate MS treatment. Other important things to keep in mind include cost, convenience, caregiver preference, and experience.
Early initiation of treatment is important, as irreversible axonal damage may occur early in the course of the disease3. Also, available therapies are more effective at preventing the formation of new lesions than repairing lesions that are already present. As the disease progresses, the autoimmune response may become increasingly difficult to suppress. The National Multiple Sclerosis Society recommends initiating treatment at the time of diagnosis4. Immunosuppressive therapies have positive clinical effects, but they only slow the course of the disease, and their use is dangerous to the patient’s overall health beyond a year or two. Currently available and FDA-approved MS drugs include:
Beta interferons: Represent the first-line treatment for relapsing-remitting MS. The exact mechanism of action is unknown, but they inhibit the pro-inflammatory cascade. Beta interferons reduce inflammatory lesions by 50 to 80%, and improve quality of life and cognitive function. Adverse effects include flu-like symptoms, injection-site reactions, elevated liver enzymes, and worsening spasticity. Beta interferons should be used with caution in patients with uncontrolled depression, for whom glatiramer acetate (Copaxone) may be considered.
- Interferon β-1b (Betaseron, Extavia): A subcutaneous injection self-administered every other day.
- Interferon beta-1a (Avonex, Rebif): Avonex is available as an intramuscular injection.
- Rebidose: A subcutaneous single-use auto injector of Interferon β-1a (Rebif) approved by the FDA in January 2013 for patients with relapsing forms of MS5.
Fingolimod (Gilenya): The first oral therapy approved to reduce the frequency of acute exacerbations and to delay physical disability for patients with MS6. Fingolimod is associated with bradycardia and prolonged QT syndrome.
Teriflunomide (Aubagio): An oral pyrimidine synthesis inhibitor that has been shown to delay onset of disease, improve neurologic function, and significantly reduce the annual relapse rates for MS patients7. Black box warnings include hepatotoxicity and teratogenicity.
Dimethyl fumarate (Tecfidera): Activates a cellular defense against oxidative stress. Dimethyl fumarate reduces the annual relapse rate, slows disability progression, and reduces MRI lesions.
Glatiramer acetate (Copaxone): A polypeptide involved in immune process modification in the pathogenesis of MS. It has been shown to decrease the rate of acute exacerbations by 29% in patients with SPMS and is approved to reduce their frequency.
Natalizumab (Tysabri): This monotherapy delays physical disability and decreases frequency of acute attacks. Natalizumab is associated with progressive multifocal leukoencephalopathy and is available only via a restricted prescribing program called TOUCH .
Methotrexate: An immunomodulator used for rheumatoid arthritis, it has been shown to delay impairment of upper extremity function in MS8.
Acute Exacerbations Management
IV steroids: High-dose IV steroids are the standard treatment in acute exacerbation of MS and have been found to be more effective than oral steroids9. Methylprednisolone (Solu-Medrol) is most commonly used, followed by prednisone taper.
Emergent plasmapheresis10: Plasmapheresis is a therapeutic plasma exchange. It is reserved for patients in acute episodes of demyelination who are resistant to steroids or when contraindications to steroid treatment exist .
Treatment for Aggressive MS
Cyclophosphamide (Cytoxan): Has been found to be the most effective treatment for aggressive MS in patients younger than 40. High-dose cyclophosphamide has been used for induction therapy to decrease relapses, disease progression, and MRI lesions in aggressive MS11.
Mitoxantrone (Novantrone): Mitoxantrone is a chemotherapeutic agent approved for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary progressive MS, but it is also approved for primary relapsing MS or worsening relapsing remitting MS. Mitoxantrone should be considered for patients with aggressive MS who have failed other treatments.
Common symptoms that are disruptive to patients and their available treatments include:
- Spasticity: Affects 90% of MS patients during their lifetime. Treatments include: baclofen, benzodiazepines, dantrolene sodium, tizanidine and gabapentin. For refractory cases: IM botulinum toxin, phenol nerve blocks, and intrathecal baclofen pump placement.
- Pain: Tricyclic antidepressants, anticonvulsants (such as phenytoin, gabapentin, and carbamazepine). For secondary pain: NSAIDs and other analgesics can be used; narcotics are not recommended.
- Sexual dysfunction: Mainstay treatments include oral phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil) or penile prostheses.
- Optic neuritis: Intravenous methylprednisolone (IVMP) may hasten recovery of visual function12.
- Heat intolerance: Fever should be treated aggressively with antipyretics; other approaches to heat intolerance are non-pharmacologic.
- Gait disturbances: The only FDA-approved drug shown to improve motor function in MS is dalfampridine (Ampyra)13.
- Bladder dysfunction: Non-pharmacologic interventions, anticholinergic medications (oxybutynin), botulinum toxin A (Botox), intermittent catheterization or alpha-blockers (Prazosin).
- Bowel dysfunction: Adopting a consistent bowel program, stool softeners, bulk formers, laxatives, rectal suppositories.
- Tremor: A difficult symptom to manage for MS patients; there is currently no adequate treatment.
- Fatigue: There are no FDA-approved treatments, but off-label options include: amantadine, methylphenidate, fluoxetine, modafinil, armodafinil.
- Depression: Selective serotonin reuptake inhibitors are first-line treatment, tricyclic antidepressants are second-line.
- Cognitive dysfunction: Treatment is supportive with speech and occupational therapy.
Comprehensive MS management includes referral to physical and occupational therapy as well as speech therapy. Speech therapy assesses language and swallowing abilities in addition to speech, helping patients acquire compensatory techniques to manage cognitive problems.
Physical therapy: Evaluates and assesses gross motor skills, such as ambulation, and provide training for assistive devices to improve motor function. Physical therapists train patients to decrease spasticity, maintain range of motion, improve motor coordination, and gain muscle strength with appropriate exercises. Exercises for spasticity include stretching programs such as water therapy and yoga. Non-pharmacologic treatment for primary pain include transcutaneous nerve stimulation and use of imagery. Secondary pain can be alleviated with moist heat, physical therapy, and stretching exercises.
Occupational therapy: Therapists assess patients’ abilities to complete activities of daily living, assess fine motor skills, and evaluate assistive technology needs. Therapists can also provide new approaches to cognitive dysfunction including cognitive retraining, mentally stimulating exercises, and compensatory strategies. Compensatory mechanisms teach patients to use their strengths to compensate for areas of weakness such as having a regular daily routine or organizing their home or office. Educational training for patients with cognitive dysfunction should be provided when fatigue is not an issue and should involve family and caregivers.
Vitamin D: There is epidemiological and experimental evidence that high levels of vitamin D may lower the risk of MS14. Additionally, high vitamin D levels may decrease relapse rate and the likelihood of conversion from CIS to MS. Optimal vitamin D concentrations for MS patients are 75-100nmol/L15. Recommended dosage for supplemental vitamin D is 500–800 IU daily.
Disease monitoring: Patients should follow up yearly with their provider, earlier if they are receiving therapy with certain medications such as fingolimod (cardiac function evaluation) or teriflunomide (hepatic function evaluation).
Vaccination: There is a concern that vaccination may trigger the onset of MS or relapses, but most killed-virus vaccines studied are safe for MS patients. According to the CDC, the following vaccinations are not linked to increased risk of developing MS: hepatitis B, tetanus, measles, influenza, and rubella16. MS specialists advise against live-attenuated vaccines for MS patients. For instance, injectable influenza vaccine has been found to be safe, but the nasal spray (FluMist), which is a live vaccine, is not recommended. Similarly, varicella-zoster vaccine (Zostavax), a live-attenuated vaccine, is safe for patients with a history of chicken pox or with a positive antibody test.
Comprehensive care: It is important to realize that due to the wide spectrum of clinical presentation, MS patients need customized care, and this may require multiple specialty consultations. Most common referrals include:
- Neuropsychology: to obtain a baseline for patients with cognitive dysfunction
- Urology: may be necessary for patients with incontinence
- Ophthalmology: for patients presenting with optic neuritis or other eye complaints
- Nephrology: consult may be necessary, especially for patients undergoing treatment with dalfampridine or teriflunomide
- Speech therapy
- Otolaryngology: to rule out laryngeal lesions for patients with dysphonia and swallowing difficulties
MS patients present a unique challenge because in addition to a multidisciplinary approach, they may also require social services involvement as their disease progresses and their disabilities accumulate. Comprehensive care including familial, social, and emotional support is of the upmost importance.