eMedicine Specialties > Ophthalmology > Neurologic Disorders

Multiple Sclerosis: Treatment & Medication

Author: Andrew G Lee, MD, Chair, Department of Ophthalmology, The Methodist Hospital; Professor of Ophthalmology, Weill Medical College of Cornell University; Adjunct Professor of Ophthalmology, the University of Iowa
Coauthor(s): Fiona Costello, MD, FRCP, Assistant Professor, Departments of Clinical Neurosciences, Neuro-ophthalmologist, Clinical Neurologist and Clinical Investigator, University of Calgary, Hotchkiss Brain Institute; Cecil L Berlie, MD, Consulting Staff, Department of Ophthalmology, Luther Midelfort Eye Clinic
Contributor Information and Disclosures

Updated: Feb 10, 2010

Treatment

Medical Care

The ONTT was designed to compare the speed and level of visual recovery between patients treated with oral prednisone, intravenous (IV) methylprednisolone (IVMP), or placebo. Patients were randomized into 1 of 3 groups within 8 days of symptom onset. Those treated with oral prednisone (1 mg/kg/d for 14 d) demonstrated an increased incidence of recurrent optic neuritis (ON) compared with those treated with IVMP (250 mg every 6 h for 3 d followed by an oral taper) or placebo.

The ONTT provides class I evidence (ie, randomized clinical trial) for recommended treatment of patients with ON. The ONTT results suggest that IV steroids, oral steroids, and placebo all result in recovery of visual function over time. IV steroids hasten the rate of recovery but do not change the final visual outcome. In the ONTT, IV steroids seemed to decrease the incidence of the development of multiple sclerosis (MS) over a 2-year period, but this effect was not sustained after year 3.

Although all 3 treatment arms of the study had equal visual outcomes, oral prednisone in conventional doses increased the likelihood for a recurrent episode of ON and is not recommended. Higher doses of oral methylprednisolone have not produced similar increased recurrence rates of ON, but the number of patients in these studies was small.

Newer studies have supported the benefit of using immunomodulatory agents (eg, interferon beta-1) in the reduction of clinically definite MS (CDMS).

The role for disease modifying agents in the treatment of ON is not to expedite the recovery of optic nerve function, which tends to be good, but rather to impact the risk of future MS. Three studies have addressed the role of interferon therapy for acute monosymptomatic ON and the future development of CDMS.

The first of these studies was the Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS), in which patients with a single clinically isolated neurologic event (ie, ON, brainstem or cerebellar syndrome, incomplete transverse myelitis) were enrolled into a randomized, placebo-controlled trial if they had 2 or more clinically silent lesions on a cranial MRI.15,16 After initial treatment with high-dose IVMP, one half of the patients received weekly interferon beta-1a (30 mcg once per week), and one half of the patients received placebo. The primary endpoint was the development of CDMS, and the secondary endpoint was the brain MRI. This study demonstrated a significantly lower rate (44%) of development of CDMS among the treatment group, and a relative reduction of new lesions in the cranial MRI among patients treated with interferon versus the placebo group.

A second study, the Early Treatment of MS (ETOMS) trial enrolled a similar group of patients, with 4 asymptomatic white matter lesions (or 3 lesions if one enhanced with gadolinium) present on the cranial MRI at presentation. One half of the patients received subcutaneous interferon beta-1a (22 mcg once per week), and one half of the patients received placebo. After 2 years, the odds ratio for the development of CDMS was 0.61 (95% confidence interval [CI] 0.37-0.99; p=0.045) in the treatment group versus the control group. More specifically, 45% of the placebo group developed CDMS after 2 years as compared to 34% of the treatment group. During the treatment study period, the MRI activity and burden of disease measured by MRI were significantly reduced in the treatment group.

In the third and most recent study, the Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) trial looked at the role of disease modifying therapy in patients with clinically isolated syndromes (either monofocal or multifocal) and at least 2 clinically silent brain MRI lesions. Subjects were randomized to receive 250 mcg of interferon beta-1b subcutaneously on alternate days or placebo until CDMS was diagnosed or the study period of 24 months was reached. Overall, interferon beta-1b delayed the time to diagnosis of MS by clinical and McDonald criteria.

Consultations

Patients with ON, particularly those with abnormal MRI findings, should be offered the opportunity to consult with a neurologist regarding the possibility of MS.

Activity

Patients with ON should be cautioned to avoid work and other activities that may require greater visual skills than they possess. Machinery, heavy equipment, sharp instruments, and other visually demanding activities might have to be avoided until they recover sufficient vision, stereovision, color vision, and contrast acuities.

Patients should know that vigorous physical activity, hot baths, and other activities that raise their core body temperature might result in temporary decreases in vision because of the Uhthoff phenomenon.

Medication

Although corticosteroids are known to have multiple short-term and long-term adverse effects, in general, a day course of IVMP followed by an oral taper over 10-14 days does not produce significant or permanent adverse effects in otherwise healthy young patients.

Corticosteroids

These agents have both anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. Glucocorticoids have profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.


Methylprednisolone (Solu-Medrol, Adlone, Medrol)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Adult

250 mg IV q6h for 3 d

Pediatric

Administer as in adults

Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adverse effects include hypertension, depression, mania, pseudotumor cerebri, meningitis, psychosis, seizures, pancreatitis, ulcer exacerbation, GI bleeding, peritonitis, toxic megacolon, hyperglycemia, adrenal suppression, Cushing syndrome, growth retardation, hyperlipidemia, cataracts, glaucoma, toxoplasmosis reactivation, TB reactivation, osteoporosis, hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections


Prednisone (Deltasone, Orasone, Meticorten)

Should only be used in conjunction with IV methylprednisolone.

Adult

1 mg/kg/d PO for 11 d

Pediatric

Administer as in adults

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in mania and depression, GI distress and bleeding, Cushing syndrome, or poor wound healing; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Interferons

These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha, beta, and gamma interferons may be given topically, systemically, and intralesionally.


Interferon beta-1a (Avonex, Rebif)

For treatment of relapsing remitting MS. Believed to act via ability to counteract cell surface expression of proinflammatory or proadhesion molecules on immune cells, among other effects. More studies needed to fully understand mechanisms of action. Only differs from interferon beta-1b in that it has amino acid sequence identical to that of natural compound and is glycosylated. Presence of glycosylation may lead to structural stability and presumably to higher biological potency. Interferons act through common receptor that activates Jak/Stat pathway of signal transduction molecules, which, in turn, lead to activation of interferon-responsive genes. Interferon beta may decrease expression of B7-1 (a proinflammatory molecule) on surface of immune cells and increase levels of TGF-beta (anti-inflammatory) in circulation of patients with MS.

Adult

Avonex: 30 mcg IM qwk
Rebif: 44 mcg SC 3 times/wk (at least 48 h between each dose)

Pediatric

Not established

Hematologic abnormalities, including anemia, thrombocytopenia, and development of agranulocytopenia, may occur when administered concomitantly with ACE inhibitors; may increase anticoagulant effects of warfarin; may increase toxicity of zidovudine

Documented hypersensitivity; liver dysfunction; severe leucopenia; thrombocytopenia; lactation

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in preexisting seizure disorder; cases of exacerbation of thyroid dysfunction have been described; caution when using interferon beta-1a in patients with uncontrolled thyroid dysfunction; besides a flulike illness, patients may experience injection-site skin reactions; interferons are abortifacient; data on teratogenicity are limited; extreme caution in patients with severe depression

Antibiotics

These agents are used for suspected bacterial infections.


Tobramycin 0.3% ophthalmic (AK Tob, Tobrex)

Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits, which results in a defective bacterial cell membrane. Available as a solution, ointment, and lotion.

Adult

1-2 gtt instilled in the eye q4h while awake for 5 d

Pediatric

<2 years: Not established
>2 years: Administer as in adults

Effects decrease when used concurrently with gentamicin

Documented hypersensitivity; mycobacterial, viral, and fungal infections of the eye; steroid combinations after uncomplicated removal of a foreign body from cornea

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use in deep-seated ocular infections or in those that may become systemic; prolonged use of antibiotics may result in bacterial or fungal overgrowth of nonsusceptible organisms

More on Multiple Sclerosis

Overview: Multiple Sclerosis
Differential Diagnoses & Workup: Multiple Sclerosis
Treatment & Medication: Multiple Sclerosis
Follow-up: Multiple Sclerosis
Multimedia: Multiple Sclerosis
References
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Further Reading

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Keywords

multiple sclerosis, MS, neurologic disorder, optic neuritis, optic nerve, nystagmus, internuclear ophthalmoplegia, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, primary progressive multiple sclerosis, treatment, symptoms

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Contributor Information and Disclosures

Author

Andrew G Lee, MD, Chair, Department of Ophthalmology, The Methodist Hospital; Professor of Ophthalmology, Weill Medical College of Cornell University; Adjunct Professor of Ophthalmology, the University of Iowa
Andrew G Lee, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Geriatrics Society, and North American Neuro-Ophthalmology Society
Disclosure: Speaker bureau Honoraria Speaking and teaching

Coauthor(s)

Fiona Costello, MD, FRCP, Assistant Professor, Departments of Clinical Neurosciences, Neuro-ophthalmologist, Clinical Neurologist and Clinical Investigator, University of Calgary, Hotchkiss Brain Institute
Fiona Costello, MD, FRCP is a member of the following medical societies: Alberta Medical Association, American Academy of Neurology, American Academy of Ophthalmology, American Medical Association, Canadian Medical Protective Association, College of Physicians and Surgeons of Alberta, North American Neuro-Ophthalmology Society, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Cecil L Berlie, MD, Consulting Staff, Department of Ophthalmology, Luther Midelfort Eye Clinic
Cecil L Berlie, MD is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Andrew W Lawton, MD, Medical Director of Neuro-Ophthalmology Service, Section of Ophthalmology, Baptist Eye Center, Baptist Health Medical Center
Andrew W Lawton, MD is a member of the following medical societies: American Academy of Ophthalmology, Arkansas Medical Society, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Brian R Younge, MD, Professor of Ophthalmology, Mayo Clinic School of Medicine
Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society
Disclosure: Nothing to disclose.

CME Editor

Ralph Garzia, OD, Assistant Dean for Clinical Programs, Associate Professor, School of Optometry, University of Missouri at St Louis
Ralph Garzia, OD is a member of the following medical societies: American Academy of Optometry and American Optometric Association
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

 
 
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