Multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

(MS) is a chronic inflammatory

demyelinating disease A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency i ...

that affects the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

(CNS). Several therapies for it exist, although there is no known cure. The most common initial course of the disease is the relapsing-remitting subtype, which is characterized by unpredictable attacks (

relapse In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or r ...

s) followed by periods of relative remission with no new signs of disease activity. After some years, many of the people who have this subtype begin to experience neurologic decline without acute relapses. When this happens it is called secondary progressive multiple sclerosis. Other, less common, courses of the disease are the primary progressive (decline from the beginning without attacks) and the progressive-relapsing (steady neurologic decline and superimposed attacks). Different therapies are used for patients experiencing acute attacks, for patients who have the relapsing-remitting subtype, for patients who have the progressive subtypes, for patients without a diagnosis of MS who have a demyelinating event, and for managing the various consequences of MS. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of MS may have several

adverse effects An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...

, and many possible therapies are still under investigation. At the same time different

alternative treatments Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability, or evidence from clinical trials. Complementary medicine (CM), complementary and alt ...

are pursued by many people, despite the fact that there is little supporting, comparable, replicated scientific study. Stem cell therapy is being studied. This article focuses on therapies for standard MS; borderline forms of MS have particular treatments that are excluded.

Acute attacks

Administration of high doses of

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...

s, such as

methylprednisolone Methylprednisolone (Depo-Medrol, Medrol, Solu-Medrol) is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used concomitantly at high ...

, is the routine therapy for acute relapses. This is administered over a period of three to five days, and has a well-established

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...

in promoting a faster recovery from

disability Disability is the experience of any condition that makes it more difficult for a person to do certain activities or have equitable access within a given society. Disabilities may be Cognitive disability, cognitive, Developmental disability, dev ...

after an attack. There is however insufficient evidence to indicate any significant impact on long-term disability of corticosteroid treatments. Steroids administered orally have a similar effectiveness and safety profile at treating MS symptoms as intravenous treatment. Consequences of severe attacks which do not respond to corticosteroids might be treated by

plasmapheresis Plasmapheresis (from the Greek πλάσμα, ''plasma'', something molded, and ἀφαίρεσις ''aphairesis'', taking away) is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the blood circulati ...

Disease-modifying treatments

, several

disease-modifying treatment A disease-modifying treatment, disease-modifying drug, or disease-modifying therapy is a treatment that delays or slows the progression of a disease by targeting its underlying cause. They are distinguished from symptomatic treatments that treat th ...

s have been approved by regulatory agencies of different countries, including the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA), the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA) and the

Pharmaceuticals and Medical Devices Agency The (PhMDA) is an Independent Administrative Institution responsible for ensuring the safety, efficacy and quality of pharmaceuticals and medical devices in Japan. It is similar in function to the Food and Drug Administration in the United State ...

(PMDA) of the Japanese

Ministry of Health, Labour and Welfare The is a cabinet level ministry of the Japanese government. It is commonly known as in Japan. The ministry provides services on health, labour and welfare. It was formed with the merger of the former Ministry of Health and Welfare or and the ...

. Medications approved by the FDA include: interferons beta-1a and beta-1b, monoclonal antibodies:

natalizumab Natalizumab, sold under the brand name Tysabri among others, is a medication used to treat multiple sclerosis and Crohn's disease. It is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin. It is given by intravenou ...

alemtuzumab Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia (CLL) and multiple sclerosis. In CLL, it has been used as both a first line and second line treatment. In MS it ...

ocrelizumab Ocrelizumab, sold under the brand name Ocrevus, is a medication used for the treatment of multiple sclerosis (MS). It is a humanized anti-CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and hence is an immunosuppressive drug. O ...

, and immunomodulators:

glatiramer acetate Glatiramer acetate (also known as Copolymer 1, Cop-1), sold under the brand name Copaxone among others, is an immunomodulator medication used to treat multiple sclerosis. Glatiramer acetate is approved in the United States to reduce the frequency ...

mitoxantrone Mitoxantrone (INN, BAN, USAN; also known as Mitozantrone in Australia; trade name Novantrone) is an anthracenedione antineoplastic agent. Uses Mitoxantrone is used to treat certain types of cancer, mostly acute myeloid leukemia. It improves the ...

fingolimod Fingolimod, sold under the brand name Gilenya, is an immunomodulating medication, mostly used for treating multiple sclerosis (MS). Fingolimod is a sphingosine-1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, prevent ...

teriflunomide Teriflunomide, sold under the brand name Aubagio, is the active metabolite of leflunomide. Teriflunomide was investigated in the Phase III clinical trial TEMSO as a medication for multiple sclerosis (MS). The study was completed in July 2010. 2-ye ...

dimethyl fumarate Dimethyl fumarate (DMF) is the methyl ester of fumaric acid and is named after the earth smoke plant (''Fumaria officinalis''). Dimethyl fumarate combined with three other fumaric acid esters (FAEs) is solely licensed in Germany as an oral thera ...

,
and

diroximel fumarate Diroximel fumarate, sold under the brand name Vumerity, is a medication used for the treatment of relapsing forms of multiple sclerosis (MS). It acts as an immunosuppressant and anti-inflammatory drug. Its most common adverse effects are flush ...

Siponimod Siponimod, sold under the brand name Mayzent, is a selective sphingosine-1-phosphate receptor modulator for oral use that is used for multiple sclerosis (MS). It is intended for once-daily oral administration. In March 2019, it was approved in t ...

was approved in March 2019.

Cladribine Cladribine, sold under the brand name Leustatin, among others, is a medication used to treat hairy cell leukemia (leukemic reticuloendotheliosis) and B-cell chronic lymphocytic leukemia. Cladribine, sold under the brand name Mavenclad, is indicate ...

was approved in March 2019.

Ozanimod Ozanimod, sold under the brand name Zeposia, is an immunomodulatory medication for the treatment of relapsing multiple sclerosis and ulcerative colitis. It acts as a sphingosine-1-phosphate (S1P) receptor agonist, sequestering lymphocytes to p ...

was approved in March 2020.

Daclizumab Daclizumab (trade name Zinbryta) is a therapeutic humanized monoclonal antibody which was used for the treatment of adults with relapsing forms of multiple sclerosis (MS). Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor ...

, that was once approved, was later withdrawn.

Medications

In 1993, interferon beta-1b was the first drug to ever be approved for MS, being soon followed by interferon beta-1a and glatiramer acetate. Interferon beta-1a is injected either weekly (

intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...

) or three times a week (

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, ...

) depending on commercial formulations, while interferon beta-1b is injected subcutaneously every second day. In 2014, a pegylated form of interferon beta-1a was introduced with the brand name Plegridy, which is available as a subcutaneous injection.Plegridy Prescribing Information
Biogen Idec Inc. Plegridy Prescribing Information (August 2014). Retrieved on 31 October 2014 This peginterferon beta 1-a attaches polyethylene glycol to the interferon molecules allowing longer lasting biological effects in the body while decreasing the frequency of administration to once every two weeks.Peginterferon beta-1a description
National Multiple Sclerosis Society (15 August 2014). Retrieved on 27 October 2014

Interferon beta The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cyto ...

balances the expression of pro- and anti-inflammatory agents in the brain, and reduces the number of inflammatory cells that cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...

. Overall, therapy with interferon beta leads to a reduction of neuron inflammation. Moreover, it is also thought to increase the production of

nerve growth factor Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was on ...

and consequently improve neuronal survival. Glatiramer acetate is a mixture of random polymers of four amino acids which is antigenically similar to the

myelin basic protein Myelin basic protein (MBP) is a protein believed to be important in the process of myelination of nerves in the nervous system. The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly ...

, a component of the myelin sheath of nerves with which it competes for presentation to T cells . It is injected subcutaneously on a daily basis. Mitoxantrone is an

immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified in ...

also used in

cancer chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothera ...

which was approved for MS in the year 2000; whereas natalizumab is a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

that was initially approved in 2004. Both are given by intravenous infusion at monthly intervals in the case of natalizumab and every three months in the case of mitoxantrone. In 2010,

, a

sphingosine-1-phosphate receptor The sphingosine-1-phosphate receptors are a class of G protein-coupled receptors that are targets of the lipid signalling molecule Sphingosine-1-phosphate (S1P). They are divided into five subtypes: S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5. Discovery ...

modulator, became the first oral drug approved by the FDA, being followed in 2012 by

, a drug that inhibits the synthesis of

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...

and disrupts the interaction of T cells with antigen presenting cell. Fingolimod and teriflunomide are taken through a daily single dose. In 2013 one further oral drug, dimethyl fumarate -or BG12- (which is an improved version of

fumaric acid Fumaric acid is an organic compound with the formula HO2CCH=CHCO2H. A white solid, fumaric acid occurs widely in nature. It has a fruit-like taste and has been used as a food additive. Its E number is E297. The salts and esters are known as fu ...

, an already existing drug), was approved by the FDA. Another oral drug,

cladribine Cladribine, sold under the brand name Leustatin, among others, is a medication used to treat hairy cell leukemia (leukemic reticuloendotheliosis) and B-cell chronic lymphocytic leukemia. Cladribine, sold under the brand name Mavenclad, is indicate ...

, was approved in Russia and Australia in 2010. Its application was rejected by the FDA and EMEA in 2011, due to safety concerns. This led the pharmaceutical to discontinue commercialization and withdraw all marketing applications. In March 2017,

was approved in the United States for the treatment of primary progressive multiple sclerosis in adults. It is also used in adults for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. Ocrelizumab was approved for use in the European Union in January 2018. In 2019,

siponimod Siponimod, sold under the brand name Mayzent, is a selective sphingosine-1-phosphate receptor modulator for oral use that is used for multiple sclerosis (MS). It is intended for once-daily oral administration. In March 2019, it was approved in t ...

and

were approved in the United States for the treatment of secondary progressive multiple sclerosis. Siponimod was approved for use in the European Union in January 2020, for the treatment of adults with secondary progressive multiple sclerosis. Cladribine was approved for use in the European Union in August 2017, for the treatment of adults with relapsing forms of multiple sclerosis. In October 2019,

(Vumerity) was approved for medical use in the United States. In March 2020,

ozanimod Ozanimod, sold under the brand name Zeposia, is an immunomodulatory medication for the treatment of relapsing multiple sclerosis and ulcerative colitis. It acts as a sphingosine-1-phosphate (S1P) receptor agonist, sequestering lymphocytes to p ...

(Zeposia) was approved in the United States for the treatment of relapsing multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. In April 2020,

monomethyl fumarate Monomethyl fumarate, sold under the brand name Bafiertam is a medication for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, ...

(Bafiertam) was approved in the United States for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Ponesimod (Ponvory) was approved for medical use in the United States in March 2021. Ublituximab (Briumvi) was approved for medical use in the United States in December 2022.

Side effects

Both the interferons and glatiramer acetate are available only in injectable forms, and both can cause skin reactions at the injection site, specially with subcutaneous administration. Skin reactions vary greatly in their clinical presentation and may include bruising,

erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not assoc ...

, pain,

pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

, irritation, swelling and in the most extreme cases cutaneous

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

. They usually appear within the first month of treatment albeit their frequence and importance diminish after six months of use. Mild skin reactions usually do not impede treatment whereas necroses appear in around 5% of patients and lead to the discontinuation of the therapy. Also over time, a visible dent at the injection site due to the local destruction of fat tissue, known as

lipoatrophy Lipoatrophy is the term describing the localized loss of fat tissue. This may occur as a result of subcutaneous injections of insulin in the treatment of diabetes, from the use of human growth hormone or from subcutaneous injections of copaxone use ...

, may develop.

Interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten the ...

s, a subclass of

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

, are produced in the body during illnesses such as

influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...

in order to help fight the infection. They are responsible of many of the symptoms of influenza infections, including

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

, muscle aches,

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, and

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

s. Many patients report influenza-like symptoms hours after taking interferon-beta that usually improve within 24 hours, being such symptoms related to the temporary increase of cytokines. This reaction tends to disappear after 3 months of treatment and its symptoms can be treated with over-the-counter

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

s, such as

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...

, that reduce fever and pain. Another common transient secondary effect with interferon-beta is a functional deterioration of already existing symptoms of the disease. Such deterioration is similar to the one produced in MS patients due to heat, fever or stress (

Uhthoff's phenomenon Uhthoff's phenomenon (also known as Uhthoff's syndrome, Uhthoff's sign, and Uhthoff's symptom) is the worsening of neurologic symptoms in multiple sclerosis (MS) and other demyelinating diseases when the body is overheated. This may occur due to ...

), usually appears within 24 hours of treatment, is more common in the initial months of treatment, and may last several days. A symptom specially sensitive to worsening is

spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...

. Interferon-beta can also reduce numbers of

white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...

s (

leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

s (

lymphopenia Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which re ...

) and

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

s (

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

), as well as affect

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

function. In most cases these effects are non-dangerous and reversible after cessation or reduction of treatment. Nevertheless, recommendation is that all patients should be monitored through laboratory blood analyses, including

liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...

, to ensure safe use of interferons. Glatiramer acetate is generally well tolerated. The most common secondary effect with glatiramer acetate after skin problem is a post-injection reaction manifested by flushing, chest tightness, heart

palpitation Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rapi ...

s, breathlessness, and anxiety, which usually lasts less than thirty minutes and does not require additional treatment. Mitoxantrone therapy may be associated with immunosuppressive effects and

liver damage Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the sig ...

; however its most dangerous side effect is its dose-related

cardiac toxicity Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity. The heart becomes weaker and is not as efficient in pumping blood. Cardiotoxicity may be caused by chemotherapy (a usual example is th ...

. Careful adherence to the administration and monitoring

guidelines A guideline is a statement by which to determine a course of action. A guideline aims to streamline particular processes according to a set routine or sound practice. Guidelines may be issued by and used by any organization (governmental or pri ...

is therefore essential; this includes obtaining an

echocardiogram An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart. It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound. Echocardiography has become routinely used in th ...

and a

complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...

before treatment to decide whether the therapy is suitable for the patient or the risks are too great. It is recommended that mitoxantrone be discontinued at the first signs of heart damage,

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

or liver dysfunction during therapy. Heart problems (mainly

systolic dysfunction Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

) appear in over 10% of patients, while

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

prevalence is 0.8%. Soon after its approval natalizumab was withdrawn from the market by its manufacturer after it was linked with three cases of the rare but hazardous neurological condition called

progressive multifocal leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal viral disease characterized by progressive damage (''-pathy'') or inflammation of the white matter (''leuko-'') of the brain (''-encephalo-'') at multiple locations (''mu ...

(PML). PML is an

opportunistic infection An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune ...

with neurological progressive symptoms caused by the replication of the

JC virus ''Human polyomavirus 2'', commonly referred to as the JC virus or John Cunningham virus, is a type of human polyomavirus (formerly known as papovavirus). It was identified by electron microscopy in 1965 by ZuRhein and Chou, and by Silverman and ...

in the

glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...

of the brain. All 3 initial cases were taking natalizumab in combination with

interferon beta-1a Interferon beta-1a (also interferon beta 1-alpha) is a cytokine in the interferon family used to treat multiple sclerosis (MS). It is produced by mammalian cells, while interferon beta-1b is produced in modified '' E. coli''. Some research indic ...

. After a safety review the drug was returned to the market in 2006 as a monotherapy for MS under a special prescription program. As of May 2011, over 130 cases of PML had been reported, all in patients who had taken natalizumab for more than a year. While none of them had taken the drug in combination with other disease-modifying treatments, previous use of MS treatments increases the risk of PML between 3 and 4-fold. The estimated

prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...

of PML is 1.5 cases per thousand natalizumab users. Around 20% of MS patients with PML die, while most of the remaining are importantly disabled. During clinical trials fingolimod gave rise to side effects such as

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

and

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

macular edema Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye (a yellow central area of the retina) and causes it to thicken and swell ( edema). The swelling may distort a person's central vision, because the macu ...

, elevated liver enzymes or reduction in lymphocyte levels. Teriflunomide is considered a very safe drug. Nevertheless, there have been reports of liver failure, and PML. Teriflunomide is also known to be dangerous for fetal development. Most common secondary effects of dimethyl fumarate during clinical trials were flushing and gastrointestinal problems. These problems were generally mild and occurred more frequently during the first month of treatment. While dimethyl fumarate leads to a reduction in white blood cell count and levels should be monitored in patients, there were no reported cases of opportunistic infections during the clinical trials. Moreover, fumaric acid is also used to treat

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

, another autoinmune disorder, and there is long term safety data from over 14 years of use without any indication of further dangerous secondary effects. In a disproportionality analysis based on real-world adverse event reports (FAERS), none of the FDA approved DMTs was associated higher risk of cancer-related reported outcomes.

Clinically isolated syndrome

The earliest clinical presentation of RRMS is the clinically isolated syndrome (CIS), that is, a single attack of a single symptom. During a CIS, there is a subacute attack suggestive of

demyelination A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency i ...

but the patient does not fulfill the

criteria Criterion, or its plural form criteria, may refer to: General * Criterion, Oregon, a historic unincorporated community in the United States * Criterion Place, a proposed skyscraper in West Yorkshire, England * Criterion Restaurant, in London, Eng ...

for diagnosis of multiple sclerosis. Early treatment can reduce the hazard of conversion to from a first attack to clinically definite multiple sclerosis. However, it is difficult to make firm conclusions about the best treatment, especially regarding the long‐term benefit and safety of early treatment, given the lack of studies directly comparing disease modifying therapies or long-term monitoring of patient outcomes.

Relapsing-remitting MS

Medications are modestly effective at decreasing the number of attacks in RRMS and in reducing the accumulation of brain lesions, which is measured using

gadolinium Gadolinium is a chemical element with the symbol Gd and atomic number 64. Gadolinium is a silvery-white metal when oxidation is removed. It is only slightly malleable and is a ductile rare-earth element. Gadolinium reacts with atmospheric oxygen ...

- enhanced

magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...

(MRI). Interferons and glatiramer acetate are roughly equivalent, reducing relapses by approximately 30% and their safe profile make them the first-line treatments. Nevertheless, not all the patients are responsive to these therapies. It is known that 30% of MS patients are non-responsive to Beta interferon. One of the factors related to non-respondance is the presence of high levels of interferon beta neutralizing

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

. Interferon therapy, and specially interferon beta-1b, induces the production of neutralizing antibodies, usually in the second 6 months of treatment, in 5 to 30% of treated patients. Moreover, a subset of RRMS patients with specially active MS, sometimes called "rapidly worsening MS" are normally non-responders to immunomodulators and are treated with either mitoxantrone or natalizumab. Natalizumab is considered highly effective in terms of relapse rate reduction and halting disability progression, however, it is considered a second-line treatment because of the risk of adverse side-effects. Natalizumab halves the risk of relapsing when compared to interferons, having an overall efficacy of over 70%. Mitoxantrone is also highly useful to reduce attacks and disability, but it is generally not considered as a long-term therapy due to its severe cardiac toxicity. There are no official guidelines yet on the use of disease-modifying oral treatments due to their recent development. While some believe that they will probably reduce the usage of first-line treatments the long-term safety of interferons and glatiramer acetate will probably slow this trend. It has been recommended that at the moment oral treatments should be mainly offered in those cases where patients do not use existing treatments due to

needle phobia Fear of needles, known in medical literature as needle phobia, is the extreme fear of medical procedures involving injections or hypodermic needles. This can lead to avoidance of medical care, including vaccine hesitancy. It is occasionally refe ...

or other reasons such as perceived inefficacy of interferons and glatiramer acetate. They could also be used in patients taking natalizumab who have developed

antibodies and are therefore at an increased risk of PML. Dimethyl fumarate is potentially one of the most interesting oral drugs due to the long term data from use in psoriasis which points towards a very good safety profile. A 2015

Cochrane Cochrane may refer to: Places Australia *Cochrane railway station, Sydney, a railway station on the closed Ropes Creek railway line Canada * Cochrane, Alberta * Cochrane Lake, Alberta * Cochrane District, Ontario ** Cochrane, Ontario, a town wit ...

systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...

found moderate quality evidence of a reduction in the number of people with RRMS that had relapses over a two-year treatment period with dimethyl fumarate versus placebo, as well as low quality evidence of a reduction in worsening disability, and an overall need for higher quality studies with longer follow-up. The relative effectiveness of different treatments is unclear, as most have only been compared to placebo or a small number of other therapies. Direct comparisons of

interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten the ...

s and

indicate similar effects or only small differences in effects on relapse rate, disease progression and

measures. Alemtuzumab, natalizumab, and fingolimod may be more effective than other drugs in reducing relapses over the short term in people with RRMS.

Natalizumab Natalizumab, sold under the brand name Tysabri among others, is a medication used to treat multiple sclerosis and Crohn's disease. It is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin. It is given by intravenou ...

and

(

Rebif Interferon beta-1a (also interferon beta 1-alpha) is a cytokine in the interferon family used to treat multiple sclerosis (MS). It is produced by mammalian cells, while interferon beta-1b is produced in modified '' E. coli''. Some research indic ...

) may reduce relapses compared to both placebo and

(

Avonex Interferon beta-1a (also interferon beta 1-alpha) is a cytokine in the interferon family used to treat multiple sclerosis (MS). It is produced by mammalian cells, while interferon beta-1b is produced in modified '' E. coli''. Some research indic ...

) while

Interferon beta-1b Interferon beta-1b is a cytokine in the interferon family used to treat the relapsing-remitting and secondary-progressive forms of multiple sclerosis (MS). It is approved for use after the first MS event. Closely related is interferon beta 1a, als ...

(

Betaseron Interferon beta-1b is a cytokine in the interferon family used to treat the relapsing-remitting and secondary-progressive forms of multiple sclerosis (MS). It is approved for use after the first MS event. Closely related is interferon beta 1a, ...

, and

may also prevent relapses. Evidence on relative effectiveness in reducing disability progression is unclear. All medications are associated with adverse effects that may influence their risk to benefit profiles. While more studies of the long-term effects of the drugs are needed, specially for the newest treatments, existing data on the effects of interferons and glatiramer acetate indicate that early-initiated long-term therapy is safe and it is related to better outcomes.

Oral contraceptive pill Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control. Female Two types of female oral contraceptive pill, taken once per day, are widely available: * The combin ...

s have contradictory results from different studies regarding any effect of decreasing relapse rate in women with multiple sclerosis.

Multiple Sclerosis Society of Great Britain The Multiple Sclerosis Society (MS Society) is the UK's largest charity for people affected by multiple sclerosis (MS). Based in London, it has offices and local groups in England, Northern Ireland, Scotland and Wales. It gained charitable company ...

Certain medications for MS symptoms, such as

carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...

(used to treat spasms and pain) and

modafinil Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant medication used to treat sleepiness due to narcolepsy, shift work sleep disorder, and obstructive sleep apnea. While it has seen off-label ...

(used to treat fatigue) can make oral contraceptive pills less effective.

Secondary progressive MS and progressive relapsing MS

Mitoxantrone has shown positive effects in people with a secondary progressive and progressive relapsing courses. It is moderately effective in reducing the progression of the disease and the frequency of relapses in people after two years. In 2007, it was the only medication approved in the US for both secondary progressive and progressive relapsing multiple sclerosis; however, it causes dose-dependent

which limits its long-term use. It is also not approved in Europe. Natalizumab has shown efficacy and has been approved for secondary progressive MS with relapses. Studies on the use of Interferon-beta-1b in secondary progressive and progressive relapsing MS do not support that it slows progression of the disease, although it is effective in reducing the number of relapses.

Primary progressive MS

Treatment of primary progressive multiple sclerosis (PPMS) is problematic as many patients do not respond to any available therapy, and no treatment has been approved specifically for use in this form of the disease. There have been several trials investigating the efficacy of different drugs for PPMS without positive results. ,

Network meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

of 9

immunomodulator Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

and

agents suggested that there was no evidence of any being effective in preventing disability progression in people with progressive MS. Drugs tested include interferon beta, mitoxantrone, glatiramer acetate or

riluzole Riluzole is a medication used to treat amyotrophic lateral sclerosis and other motor neuron diseases. Riluzole delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. Riluzole is ...

. People with PPMS have also been included in trials of

azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...

methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...

intravenous immunoglobulin Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory dem ...

cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...

and

hematopoietic Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...

stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...

. In March 2017,

was approved in the United States for the treatment of primary progressive multiple sclerosis in adults. It is also used for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults.

Managing the effects of MS

Rehabilitation

Occupational Therapy Occupational Therapy can play an important factor in managing symptoms of multiple sclerosis. These symptoms are not limited to but include tremors, gait impairment, and difficulty with transfers. OT's can help manage tremors by outfitting the patient using small passive weights to decrease the intensity of the tremors. With regard to gait impairment, occupational therapists can help develop a specific gait training program, evaluate for the most appropriate adaptive equipment and devices, and consider the need for powered mobility. Occupational Therapists are skilled in transferring and can help those with multiple sclerosis with their transferring abilities as well as providing training on transferring techniques and evaluation of assistive devices.

Physical therapy

Symptoms of MS that can be improved include

, depression, bladder dysfunction, and neurological symptoms. These symptoms can be improved by physical therapy and medication. Physical therapists can show strengthening exercises and ways to stretch; ultimately making daily tasks easier and reduces fatigue while muscle strength increases as flexibility increases. Exercise therapy can be proscribed safely without increased relapse risk, and is the best supported rehabilitation intervention for reducing fatigue and improving muscle strength, mobility and quality of life according to an overview of Cochrane systematic reviews for rehabilitation. Both drug therapy and

neurorehabilitation Neurorehabilitation is a complex medical process which aims to aid recovery from a nervous system injury, and to minimize and/or compensate for any functional alterations resulting from it. Features In case of a serious disability, such as caused ...

have shown to ease the burden of some symptoms, even though neither influence disease progression. For other symptoms the efficacy of treatments is still very limited. Aquatic therapy has also been shown to alleviate symptoms of multiple sclerosis. Aquatic cycling and aerobic exercise is a safe and effective way to increase muscular strength, endurance, and circulation in MS patients. Aquatic therapy has decreased patient's pain, aided in depression/fatigue, and improved cardiorespiratory fitness. Overall, this modality has beneficial impacts on daily life activities and quality of life.

Neurorehabilitation

Although there are relatively few studies of rehabilitation in MS, its general effectiveness, when conducted by a team of specialists, has been clearly demonstrated in other diseases such as

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

head trauma A head injury is any injury that results in trauma to the skull or brain. The terms ''traumatic brain injury'' and ''head injury'' are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of inju ...

. As for any patient with neurologic deficits, a

multidisciplinary Interdisciplinarity or interdisciplinary studies involves the combination of multiple academic disciplines into one activity (e.g., a research project). It draws knowledge from several other fields like sociology, anthropology, psychology, ec ...

approach is key to limiting and overcoming disability; however there are particular difficulties in specifying a 'core team' because people with MS may need help from almost any health profession or service at some point.

Neurologist Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal c ...

s are mainly involved in the diagnosis and ongoing management of multiple sclerosis, and any exacerbations. The comprehensive rehabilitation process for patients with multiple sclerosis is generally managed by

physiatrist Physical medicine and rehabilitation, also known as physiatry, is a branch of medicine that aims to enhance and restore functional ability and quality of life to people with physical impairments or disabilities. This can include conditions su ...

s. Allied treatments such as

physiotherapy Physical therapy (PT), also known as physiotherapy, is one of the allied health professions. It is provided by physical therapists who promote, maintain, or restore health through physical examination, diagnosis, management, prognosis, patient ...

speech and language therapy Speech is a human vocal communication using language. Each language uses phonetic combinations of vowel and consonant sounds that form the sound of its words (that is, all English words sound different from all French words, even if they are th ...

occupational therapy Occupational therapy (OT) is a global healthcare profession. It involves the use of assessment and intervention to develop, recover, or maintain the meaningful activities, or ''occupations'', of individuals, groups, or communities. The field of ...

can also help to manage some symptoms and maintain

quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...

. Treatment of

neuropsychiatric Neuropsychiatry or Organic Psychiatry is a branch of medicine that deals with psychiatry as it relates to neurology, in an effort to understand and attribute behavior to the interaction of neurobiology and social psychology factors. Within neurop ...

symptoms such as emotional distress and

clinical depression Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...

should involve

mental health Mental health encompasses emotional, psychological, and social well-being, influencing cognition, perception, and behavior. It likewise determines how an individual handles stress, interpersonal relationships, and decision-making. Mental health ...

professionals such as

therapist Therapist is a person who offers any kinds of therapy. Therapists are trained professionals in the field of any types of services like psychologists, social workers, counsellors, life coachers and others. They are helpful in counselling individuals ...

psychologist A psychologist is a professional who practices psychology and studies mental states, perceptual, cognitive, emotional, and social processes and behavior. Their work often involves the experimentation, observation, and interpretation of how indi ...

s, and

psychiatrist A psychiatrist is a physician who specializes in psychiatry, the branch of medicine devoted to the diagnosis, prevention, study, and treatment of mental disorders. Psychiatrists are physicians and evaluate patients to determine whether their sy ...

s, while

neuropsychologist Neuropsychology is a branch of psychology concerned with how a person's cognition and behavior are related to the brain and the rest of the nervous system. Professionals in this branch of psychology often focus on how injuries or illnesses of t ...

s can help to evaluate and manage

cognitive deficit Cognitive deficit is an inclusive term to describe any characteristic that acts as a barrier to the cognition process. The term may describe * deficits in overall intelligence (as with intellectual disabilities), * specific and restricted defici ...

s. Multidisciplinary approaches have been shown to be effective in increasing activity levels and participation in multiple sclerosis. Studies investigating information provision in support of patient understanding and participation suggest that while interventions (written information, decision aids, coaching, educational programmes) may increase patient knowledge, the evidence of an effect on decision making and quality of life is mixed and low certainty. Due to the paucity of randomized controlled studies, there is limited evidence of the overall efficacy of individual therapy disciplines, though there is good evidence that specific approaches, such as exercise, psychology therapies, particularly cognitive behavioral approaches and energy conservation instruction are effective. More specifically psychological interventions seem useful in the treatment of depression, while evidence on effectiveness for other uses such as the treatment of cognitive impairments or vocational counseling is less strong. Cognitive training, alone or combined with other neuropsychological interventions, may show positive effects for memory and attention though firm conclusions are not possible given small sample numbers, variable methodology, interventions and outcome measures. The effectiveness of palliative approaches in addition to standard care is uncertain, due to lack of evidence. It is difficult to be specific about what types of rehabilitation will be most beneficial because therapies are tailored to meet the individual's specific needs. In regards to well-being, physical therapy focused on gait training can be vital to maximizing MS patient participation via reduction of fatigue during walking and

activities of daily living Activity may refer to: * Action (philosophy), in general * Human activity: human behavior, in sociology behavior may refer to all basic human actions, economics may study human economic activities and along with cybernetics and psychology may st ...

(ADLs). Most gait training is performed over-ground (i.e., in a gym room or outside on uneven ground), on treadmills or, less commonly, using robotic-assisted devices. Robotic-assisted body weight-supported treadmill training may be an effective therapeutic option in MS patients with severe walking impairments. In contrast, over-ground gait training may be most effective in improving gait speed in MS patients with less severe impairments. Equine-assisted therapies such as

therapeutic horseback riding Equine-assisted therapy (EAT) encompasses a range of treatments that involve activities with horses and other equines to promote human physical and mental health. The use of EAT has roots in antiquity, and EAT applies to physical health issues in ...

and

hippotherapy Equine-assisted therapy (EAT) encompasses a range of treatments that involve activities with horses and other Equinae, equines to promote human physical and mental health. The use of EAT has roots in Ancient history, antiquity, and EAT applies to ...

are additional treatments that can positively influence gait, balance and quality of life in people with MS. Another effective modality used in physical therapy to improve gait and balance for MS patients is

aquatic therapy Aquatic therapy refers to treatments and exercises performed in water for relaxation, fitness, physical rehabilitation, and other therapeutic benefit. Typically a qualified aquatic therapist gives constant attendance to a person receiving treat ...

. Patients with MS can perform walking, functional exercises, balance training and stretches in aquatic therapy to improve overall gait performance. Aquatic therapy can not only improve gait for MS patients but also dynamic balance and postural stability. Historically, individuals with MS were advised against participation in physical activity due to worsening symptoms. However, under the direction of an expert, participation in physical activity can be safe and has been proven beneficial for persons with MS. Research has supported the rehabilitative role of physical activity in improving muscle power, mobility, mood, bowel health, general conditioning and quality of life. The effectiveness of interventions, including exercise, specifically for the prevention of falls in people with MS is uncertain, while there is some evidence of an effect on balance function and mobility. Depending on the person, activities may include resistance training, walking, swimming, yoga, tai chi, and others. Determining an appropriate and safe exercise program is challenging and must be carefully individualized to each person being sure to account for all

contraindications In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...

and precautions. An elevated core temperature, leading to increased symptom presentation has been noted during exercise, due to variations in circadian body temperature throughout the day, and due to heat exposure including warm temperatures, warm showers, sun bathing, etc. Care should be taken not to overheat a person with MS during the course of exercise. There is some evidence that cooling measures are effective in allowing a greater degree of exercise: cold showers, cold water limb immersion, applying ice packs, and drinking cold beverages. These strategies are effective when attempting to decrease core temperature post-exercise, and as a method of pre-cooling prior to physical activity or heat exposure. On 26 March 2021, the U.S.

(FDA) authorized marketing of a new device indicated for use as a short-term treatment of gait deficit due to mild to moderate symptoms from multiple sclerosis (MS). The device is intended to be used by prescription only as an adjunct to a supervised therapeutic exercise program in patients 22 years of age and older. The device, called Portable Neuromodulation Stimulator (PoNS), is a neuromuscular tongue stimulator that consists of a non-implantable apparatus to generate electrical pulses for stimulation of the trigeminal and facial nerves via the tongue to provide treatment of motor deficits. The PoNS device is a portable, non-implantable device which delivers mild neuromuscular electrical stimulation to the dorsal surface of the tongue.

Medical treatments for symptoms

Multiple sclerosis can cause a variety of symptoms including changes in sensation (

hypoesthesia Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to Sensory receptor, sensory stimuli. In everyday speech this is generally r ...

), muscle weakness, abnormal muscle spasms, impaired movement, difficulties with coordination and balance, problems in speech (known as

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectively ...

) or swallowing (

dysphagia Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a disease#Terminology, condition in its own right. It may be a sensation that suggests difficulty in the passag ...

), visual problems (

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

optic neuritis Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes. It is also known as optic papillitis (when the head of the optic nerv ...

, or

diplopia Diplopia is the simultaneous perception of two images of a single object that may be displaced horizontally or vertically in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often v ...

and acute or chronic

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

syndromes,

bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...

and

bowel The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

difficulties, cognitive impairment, or emotional symptoms (mainly depression). At the same time for each symptom there are different treatment options. * Bladder: Symptomatology of the

urinary tract The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, con ...

is common in MS. Treatments for

problems vary depending on the origin or type of dysfunction but can mainly divided into treatment of bladder control and

incontinence Incontinence or Incontinent may refer to: *Fecal incontinence, the involuntary excretion of bowel contents *Urinary incontinence, the involuntary excretion of urine * Lack of moderation or self-control, especially related to sexual desire - see I ...

, and of

urinary tract infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

s. Regarding bladder control, some examples of medications used are

desmopressin Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels. In hemophilia A and von Willebrand disease, it should on ...

for

nocturia Nocturia is defined by the International Continence Society (ICS) as “the complaint that the individual has to wake at night one or more times for voiding (''i.e. to urinate'').” The term is derived from Latin ''nox, night'', and Greek '' �αο ...

and

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

drugs such as

oxybutynin Oxybutynin, sold as under the brand names Ditropan among others, is a medication used to treat overactive bladder. It works similar to tolterodine, Darifenacin, and Solifenacin. While used for bed wetting in children, evidence to support this ...

and

tolterodine Tolterodine, sold under the brand name Detrol among others, is a medication used to treat frequent urination, urinary incontinence, or urinary urgency. Effects are seen within an hour. It is taken by mouth. Common side effects include headach ...

for

urinary urgency Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...

. Non-pharmacological management includes

pelvic floor The pelvic floor or pelvic diaphragm is composed of muscle fibers of the levator ani, the coccygeus muscle, and associated connective tissue which span the area underneath the pelvis. The pelvic diaphragm is a muscular partition formed by the lev ...

muscle training, stimulation,

pessaries A pessary is a prosthetic device inserted into the vagina for structural and pharmaceutical purposes. It is most commonly used to treat stress urinary incontinence to stop urinary leakage and to treat pelvic organ prolapse to maintain the locati ...

, bladder retraining, changes to daily life habits such as clothing, use of

external urine collection devices A urine collection device or UCD is a device that allows the collection of urine for analysis (as in medical or forensic urinalysis) or for purposes of simple elimination (as in vehicles engaged in long voyages and not equipped with toilets, pa ...

for men and

incontinence pad An incontinence pad is a small, impermeable multi-layered sheet with high absorbency that is used in the incontinence and health-care industries as a precaution against fecal or urinary incontinence. It is generally made of cotton if washable, or p ...

s for women; and sometimes intermittent

urinary catheterization In urinary catheterization a latex, polyurethane, or silicone tube known as a urinary catheter is inserted into the bladder through the urethra to allow urine to drain from the bladder for collection. It may also be used to inject liquids used ...

. Regarding long term catheterization, it is associated to urinary tract infections and should be avoided whenever possible. Some of these recommendations do not come from specific studies in MS but are general recommendations for those who have

neurogenic bladder Neurogenic bladder dysfunction, or neurogenic bladder, refers to urinary bladder problems due to disease or injury of the central nervous system or peripheral nerves involved in the control of urination. There are multiple types of neurogenic bladde ...

. * Bowel:

problems affect around 70% of the patients. Around 50% of patients have

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

and up to 30% have

fecal incontinence Fecal incontinence (FI), or in some forms encopresis, is a lack of control over defecation, leading to involuntary loss of bowel contents, both liquid stool elements and mucus, or solid feces. When this loss includes flatus (gas), it is referred ...

. Cause of bowel impairments in MS patients is usually either a reduced

gut motility Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, which ...

or an impairment in neurological control of

defecation Defecation (or defaecation) follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus. The act has a variety of names ranging f ...

. The former is commonly related to inmobility or secondary effects from drugs used in the treatment of the disease. Pain or problems with defecation can be helped with a diet change which includes among other changes an increased fluid intake, oral

laxative Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation. Laxatives vary as to how they work and the side effects they may have. Certain stimulant, lubri ...

s or

suppositories A suppository is a dosage form used to deliver medications by insertion into a body orifice where it dissolves or melts to exert local or systemic effects. There are three types of suppositories, each to insert into a different sections: rectal su ...

and

enema An enema, also known as a clyster, is an injection of fluid into the lower bowel by way of the rectum.Cullingworth, ''A Manual of Nursing, Medical and Surgical'':155 The word enema can also refer to the liquid injected, as well as to a device ...

s when habit changes and oral measures are not enough to control the problems. * Cognitive and emotional:

symptomatology is common in the course of the disease. Depression and

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

appear in up to 80% of patients,. Emotional lability leading to uncontrollable crying is also common. These symptoms can be treated with

antidepressants Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, heada ...

and

cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...

; however, high quality studies on efficacy are lacking. For example, in the specific case of antidepressants and depression, only two studies were considered worth considering by the

Cochrane collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...

and they only showed a trend towards efficacy. While non-invasive brain stimulation with techniques such as

transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse gener ...

could prove beneficial for depression in multiple sclerosis, disease specific studies have been limited and may require targeting of specific brain networks associated with depression in

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

. Other neuropsychiatric symptoms are

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

and

disinhibition In psychology, disinhibition is a lack of restraint manifested in disregard of social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive, and perceptual aspects with signs and symptom ...

. Cognitive impairment is a frequent complication of MS even after the introduction of disease-modifying treatments in the last 20 years. Although the disease is usually the primary cause of cognitive problems, other factors such as medications, relapses or depression may be enhancing them so a correct evaluation of the deficits and factors exacerbating them is important. Regarding primary deficits, data point towards administration of L-amphetamine and

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...

being useful, whereas

memantine Memantine is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth. Common side effects include headache, constipation, sleepiness, and dizziness. Severe side effects may include blood clots ...

and

anticholinesterase Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. This increases the amount of the acetylcholine or butyrylcholine in the syn ...

drugs such as

donepezil Donepezil, sold under the brand name Aricept among others, is a medication used to treat dementia of the Alzheimer's disease, Alzheimer's type. It appears to result in a small benefit in mental function and ability to function. Use, however, ha ...

—commonly used in

Alzheimer disease Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...

— are not considered effective in improving cognitive functions. The effectiveness of

cognitive rehabilitation therapy Cognitive rehabilitation refers to a wide range of evidence-based interventions designed to improve cognitive functioning in brain-injured or otherwise cognitively impaired individuals to restore normal functioning, or to compensate for cognitive ...

is less clear. For those patients with MS who have

pseudobulbar affect Pseudobulbar affect (PBA), or emotional incontinence, is a type of emotional disturbance characterized by uncontrollable episodes of crying, laughing, anger or other emotional displays. PBA occurs secondary to a neurologic disorder or brain inj ...

(PBA), characterized by uncontrollable episodes of crying and/or laughing, or other emotional displays, Dextromethorphan/quinidine can be considered as treatment as it is the only FDA approved drug for treatment for PBA, though other medications such as

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracell ...

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

s have been used in clinical practice. * Dysphagia and dysarthria:

is a difficulty with eating and swallowing which may cause

choking Choking, also known as foreign body airway obstruction (FBAO), is a phenomenon that occurs when breathing is impeded by a blockage inside of the respiratory tract. An obstruction that prevents oxygen from entering the lungs results in oxygen de ...

and aspiration of food or liquid into the

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

s, while

is a

neurological Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...

motor speech disorder Motor speech disorders are a class of speech disorders that disturb the body's natural ability to speak due to neurologic impairments. These neurologic impairments make it difficult for individuals with motor speech disorders to plan, program, co ...

characterized by poor control over the subsystems and muscles responsible for

speech Speech is a human vocal communication using language. Each language uses Phonetics, phonetic combinations of vowel and consonant sounds that form the sound of its words (that is, all English words sound different from all French words, even if ...

("articulation"). A speech and language therapist may give advice on specific swallowing techniques, on adapting food consistencies and dietary intake, on techniques to improve and maintain speech production and clarity, and on alternative communication approaches. In the case of advanced dysphagia, food can be supplied by a

nasogastric tube Nasogastric intubation is a medical process involving the insertion of a plastic tube (nasogastric tube or NG tube) through the nose, down the oesophagus, and down into the stomach. Orogastric intubation is a similar process involving the inserti ...

, which is a tube that goes through the nose directly to the stomach; or a

percutaneous endoscopic gastrostomy Percutaneous endoscopic gastrostomy (PEG) is an endoscopic medical procedure in which a tube (PEG tube) is passed into a patient's stomach through the abdominal wall, most commonly to provide a means of feeding when oral intake is not adequate (fo ...

(PEG), which is a procedure for placing a tube into the stomach and therefore administering food directly to it. * Erectile dysfunction:

erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...

is common in male patients with MS. There is some evidence indicating that

sildenafil citrate Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by ...

may be a useful treatment.

Prostaglandin E1 Prostaglandin E1 (PGE1), also known as alprostadil, is a naturally occurring prostaglandin which is used as a medication. In infants with congenital heart defects, it is delivered by slow injection into a vein to open the ductus arteriosus unti ...

has shown benefits for patients with erectile dysfunction due to a range of causes including multiple sclerosis. * Fatigue:

is very common and disabling in MS, and at the same time it has a close relationship with depressive symptomatology. When depression is reduced fatigue also tends to improve, so patients should be evaluated for depression before other therapeutic approaches are used. In a similar way, other factors such as disturbed sleep, chronic pain, poor nutrition, or even some medications can contribute to fatigue; medical professionals are therefore encouraged to identify and modify them. A few medications have been studied to treat MS-related fatigue, such as

amantadine Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended due to wid ...

pemoline Pemoline, sold under the brand name Cylert among others, is a stimulant medication which has been used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It has been discontinued in most countries to due to rare b ...

(which is a

psychostimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

also used for

attention-deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...

and

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...

), or

, as well as psychological interventions of energy conservation, but the effects of all of them are small. Fatigue is therefore a very difficult symptom to manage for which no drugs are recommended. * Pain:

acute Acute may refer to: Science and technology * Acute angle ** Acute triangle ** Acute, a leaf shape in the glossary of leaf morphology * Acute (medicine), a disease that it is of short duration and of recent onset. ** Acute toxicity, the adverse eff ...

pain is mainly due to

(with

corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...

being the best treatment available), as well as

trigeminal neuralgia Trigeminal neuralgia (TN or TGN), also called Fothergill disease, tic douloureux, or trifacial neuralgia is a long-term pain disorder that affects the trigeminal nerve, the nerve responsible for sensation in the face and motor functions such as ...

Lhermitte's sign Lhermitte phenomenon, also called the barber chair phenomenon, is an uncomfortable "electrical" sensation that runs through the back and into the limbs. The sensation can feel like it goes up or down the spine. It is painful for some, although oth ...

, or

dysesthesias Dysesthesia is an unpleasant, abnormal sense of touch. Its etymology comes from the Greek word "dys," meaning "bad," and "aesthesis," which means "sensation" (abnormal sensation). It often presents as pain Joseph J. Marbach, Joseph Marbach hypoth ...

Subacute In medicine, describing a disease as acute denotes that it is of short duration and, as a corollary of that, of recent onset. The quantification of how much time constitutes "short" and "recent" varies by disease and by context, but the core deno ...

pain is usually secondary to the disease and can be a consequence of spending too long in the same position, urinary retention, and infected skin ulcers, amongst others. Treatment will depend on cause. Chronic pain is very common and harder to treat as its most common cause is dysesthesias. Acute pain due to trigeminal neuralgia is usually successfully treated with anticonvulsants such as

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...

. Both Lhermitte's sign and painful dysesthesias usually respond to treatment with

clonazepam Clonazepam, sold under the brand names Klonopin and Rivotril, is a medication used to prevent and treat seizures, panic disorder, anxiety disorders, and the movement disorder known as akathisia. It is a tranquilizer of the benzodiazepine clas ...

, or

amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...

Sativex Nabiximols (USAN, trade name Sativex) is a specific ''Cannabis'' extract that was approved in 2010 as a botanical drug in the United Kingdom. Nabiximols is sold as a mouth spray intended to alleviate neuropathic pain, spasticity, overactive bla ...

is approved for treatment of pain in MS in different countries, but due to its derivation from

cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternatively ...

, it is currently not available in others, such as the USA. This medication is also being investigated for the management of other MS symptoms, such as spasticity, and has shown long-term safety and efficacy. The evidence for the effectiveness of non-pharmacological interventions for chronic pain is limited, very low quality and insufficient to recommend such interventions alone, however their use in combination with pharmacological agents may be reasonable. * Spasticity:

is characterized by increased stiffness and slowness in

limb Limb may refer to: Science and technology *Limb (anatomy), an appendage of a human or animal *Limb, a large or main branch of a tree *Limb, in astronomy, the curved edge of the apparent disk of a celestial body, e.g. lunar limb *Limb, in botany, ...

movement, the development of certain postures, an association with weakness of voluntary

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

power, and with involuntary and sometimes painful

spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle c ...

s of limbs. A physiotherapist can help to reduce spasticity and avoid the development of

contracture In pathology, a contracture is a permanent shortening of a muscle or joint. It is usually in response to prolonged hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions like spasti ...

s with techniques such as passive stretching.

Nabiximols Nabiximols (United States Adopted Name, USAN, trade name Sativex) is a specific ''Cannabis'' extract that was approved in 2010 as a botanical drug in the United Kingdom. Nabiximols is sold as a mouth spray intended to alleviate neuropathic pain, ...

is safe and effective for relieving spasticity. There is evidence, albeit limited, of the clinical effectiveness of

baclofen Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...

dantrolene Dantrolene sodium, sold under the brand name Dantrium among others, is a postsynaptic muscle relaxant that lessens excitation-contraction coupling in muscle cells. It achieves this by inhibiting Ca2+ ions release from sarcoplasmic reticulum s ...

diazepam Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, a ...

, and

tizanidine Tizanidine, sold under the brand name Zanaflex among others, is a medication that is used to treat muscle spasticity due to spinal cord injury or multiple sclerosis as well as spastic cerebral palsy. Effectiveness appears similar to baclofen o ...

. In the most complicated cases

intrathecal Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain man ...

injections of baclofen can be used. There are also

palliative Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...

measures like

casting Casting is a manufacturing process in which a liquid material is usually poured into a mold, which contains a hollow cavity of the desired shape, and then allowed to solidify. The solidified part is also known as a ''casting'', which is ejected ...

splints Splints is an ailment of the horse or pony, characterized by a hard, bony swelling, usually on the inside of a front leg, lying between the splint and cannon bone or on the splint bone itself. It may be "hot," meaning that it occurred recently an ...

or customized seatings. Among non-pharmacological interventions there is low level and limited evidence of a benefit for spasticity for people with multiple sclerosis for physical activity programs,

and pulsed

electromagnetic therapy Electromagnetic therapy or electromagnetic field therapy refers to therapy involving the use of magnets or electromagnets. Types include : *Bioelectromagnetics, the study of how electromagnetic fields interact with and influence biological proce ...

. Systematic review has found no evidence of benefit exists for transcutaneous electrical nerve stimulation, sports climbing and vibration therapy. * Vision: different drugs as well as optic compensatory systems and prisms can be used to improve the symptoms of

(double vision). Surgery can also be used in some cases. * Walking : dalfampridine (''ampyra'') is a broad-spectrum

potassium channel blocker Potassium channel blockers are agents which interfere with conduction through potassium channels. Medical uses Arrhythmia Potassium channel blockers used in the treatment of cardiac arrhythmia are classified as class III antiarrhythmic age ...

. It is approved by the FDA to treat walking difficulties in MS. It has been shown to increase walking speed, although its high cost (over 1000 dollars a month) limits its usage. Other symptoms, such as

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...

or sensory losses, do not have proven treatments. Evidence for an effect of respiratory muscle training is heterogeneous and low quality, while the effect on important outcomes like cough efficacy, pneumonia, and quality of life have not been evaluated.

Epileptic seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

s are a potentially serious

comorbidity In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often wikt:co-occur#Verb, co-occurring (that is, wikt:concomitant#Adjecti ...

in people in multiple sclerosis which is uncommon but nonetheless present more often than in the general population, however there is currently a lack of evidence on the efficacy and safety of anti-epileptic medication specifically in people with multiple sclerosis. possibly as a secondary result of demyelinating lesions, is an uncommon but potentially serious complaint

Research

Research directions on MS treatments include investigations of MS pathogenesis and heterogeneity; research of more effective, convenient, or tolerable new treatments for RRMS; creation of therapies for the progressive subtypes; neuroprotection strategies; and the search for effective symptomatic treatments. Advances during the last decades has led to the recent approval of several oral drugs. These drugs are expected to gain in popularity and frequency of use at the expense of previously existing therapies. Further oral drugs are still under investigation, the most notable example being

laquinimod Laquinimod is an experimental immunomodulator developed by Active Biotech and Teva. It is being investigated as an oral treatment for multiple sclerosis (MS). Laquinimod is the successor of Active Biotech's failed experimental immunomodulator li ...

, which was announced in August 2012 to be the focus of a third phase III trial after mixed results in the previous ones. Similarly, Other studies are aimed to improve efficacy and ease of use of already existing therapies through the use of novel preparations. Such is the case the

PEGylated PEGylation (or pegylation) is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol (PEG, in pharmacy called macrogol) polymer chains to molecules and macrostructures, such as a drug, therapeutic protein ...

version of interferon-β-1a, that has a longer life than normal interferon and therefore it is being studied if given at less frequent doses has a similar efficacy than the existing product. With the completion of a robust two-year study, it is shown that the PEGylated interferon beta-1a has greater efficacy in decreasing relapse rate and disability progression compared to placebo for MS patients. Preliminary data have suggested that

mycophenolate mofetil Mycophenolic acid (MPA) is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and live ...

, an anti- rejection

immunosuppressant medication Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...

, might have benefits in people with multiple sclerosis. However a

found that the limited evidence available was insufficient to determine the effects of mycophenolate mofetil as an add‐on therapy for interferon beta-1a in people with RRMS. Monoclonal antibodies, which are drugs of the same family as natalizumab, have also raised high levels of interest and research.

Alemtuzumab Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia (CLL) and multiple sclerosis. In CLL, it has been used as both a first line and second line treatment. In MS it ...

daclizumab Daclizumab (trade name Zinbryta) is a therapeutic humanized monoclonal antibody which was used for the treatment of adults with relapsing forms of multiple sclerosis (MS). Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor ...

and

CD20 B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase (CD45R+, CD117+) and progressively increasing in concentration until maturity. In humans CD20 is encoded by the ''MS4A1'' gene. This gene e ...

monoclonal antibodies such as

rituximab Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric p ...

and

ofatumumab Ofatumumab is a fully human monoclonal antibody to CD20, which appears to provide rapid B-cell depletion. Under the brand name Kesimpta, it is approved for the treatment of multiple sclerosis in the United States as well as in the European Unio ...

have all shown some benefit and are under study as potential treatments for MS. Nevertheless, their use has also been accompanied by the appearance of potentially dangerous adverse effects, most importantly opportunistic infections. Related to these investigations is the recent development of a test against

antibodies which might help to predict what patients are at a greater risk of developing progressive multifocal leukoencephalopathy when taking natalizumab. While monoclonal antibodies are probably going to have some role in the treatment of the disease in the future, it is believed that it will be small due to the risks associated to them. Another research strategy is to evaluate the combined effectiveness of two or more drugs. The main rationale for polytherapy in MS is that the involved treatments target different mechanisms of the disease and therefore their use is not necessarily exclusive. Moreover,

synergies Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts. The term ''synergy'' comes from the Attic Greek word συνεργία ' from ', , meaning "working together". History In Christian ...

, in which a drug potentiates the effect of another are also possible. Nevertheless, there can also appear important drawbacks such as antagonizing mechanisms of action or potentiation of deleterious secondary effects. While there have been several clinical trials of combined therapy none has shown positive enough effects to merit the consideration as a viable treatment for MS. Likewise, there are not any effective treatments for the progressive variants of the disease. Many of the newest drugs as well as those under development are probably going to be evaluated as therapies for PPMS or SPMS, and their improved effectiveness when compared with previously existing drugs may eventually lead to a positive result in these groups of patients. Medications that influence voltage-gated sodium ion channels are under investigation as a potential neuroprotective strategy because of hypothesized role of sodium in the pathological process leading to axonal injury and accumulating disability. Currently, there is insufficient evidence of an effect of sodium channel blockers for people with MS. There is growing developments in the area of medical imaging and MRI, allowing for better reviews and understandings of MS in patients and how to treat each case in a more effective method.

Stem cell transplant

Finally, regarding neuroprotective and specially regenerative treatments, such as

stem cell therapy Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition. , the only established therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone-marrow transplantation, but ...

, while their research is considered of high importance at the moment they are only a promise of future therapeutic approaches. A 2018 study found promising results in relapsing-remitting MS but more research is needed.

CCSVI

In 2008, vascular surgeon

Paolo Zamboni Paolo Zamboni (born 25 March 1957, Ferrara, Italy) is an Italian doctor and scientist. He is full Professor and Director of the School of Vascular Surgery at the University of Ferrara in Italy. He is known to have discovered, identified and des ...

suggested that MS involves a

vascular The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...

process he referred to as

chronic cerebrospinal venous insufficiency Chronic cerebrospinal venous insufficiency (CCSVI or CCVI) is a term invented by Italian researcher Paolo Zamboni in 2008 to describe compromised flow of blood in the veins draining the central nervous system. Zamboni hypothesized that it migh ...

(CCSVI), in which veins from the brain are constricted. He found CCSVI in all 65 patients with MS in his study. This theory received important attention in the media and among people with MS, specially in Canada. Concern has been raised with Zamboni's research as it was neither blinded nor controlled, and additionally its assumptions about the pathophisiology of the disease may not be backed by known data. Also further studies have either not found a relationship or found a much less strong one. This has raised objections to the hypothesis of CCSVI originating MS. The "liberation procedure" has been criticized for possibly resulting in serious complications and deaths while its benefits have not been proven. Currently it is recommended not to use the proposed treatment unless its effectiveness is confirmed by controlled studies. Research on CCSVI has been fast tracked but researchers have been unable to confirm whether CCSVI has a role in causing MS.

Alternative treatments

Over 50% of MS patients may use

complementary and alternative medicine Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability, or evidence from clinical trials. Complementary medicine (CM), complementary and alt ...

, although numbers vary greatly depending on the definition of alternative medicine used. In the United States, it is estimated that 75% of the MS patient populations use at least one complementary and alternative medicine for treatment and symptomatic control.Overview of CAM for management of MS
Multiple Sclerosis Treatment and Management Overview (Healthline) (28 July 2014). Retrieved on 30 October 2014 The evidence for effectiveness for such treatments in most cases is weak or absent. Examples of treatments used by patients include dietary supplementation and regimens such as vitamin D, calcium, vitamin B12, and antioxidants. The rationale behind the use of Vitamin D supplementation is that studies show an association between vitamin D deficiency and increasing progression of MS, as well as the anti-inflammatory effects of vitamin D. However available evidence suggests vitamin D supplementation, irrespective of the form and dose used, provides no apparent benefit for people with MS for measures such as relapse recurrence of, disability worsening and MRI lesions while effects on health‐related quality of life and fatigue are unclear. For antioxidant therapy, studies have shown that reactive oxidative species lead to the formation of multiple sclerosis lesions in which antioxidants can help induce neuroprotective and immunomodulatory effects. Probably the most clear disease modifying factor (for worse) is smoking, and therefore to quit smoking should be considered. Other alternative treatments include

relaxation technique A relaxation technique (also known as relaxation training) is any method, process, procedure, or activity that helps a person to relax; to attain a state of increased calmness; or otherwise reduce levels of pain, anxiety, stress or anger. Relaxa ...

s such as

yoga Yoga (; sa, योग, lit=yoke' or 'union ) is a group of physical, mental, and spiritual practices or disciplines which originated in ancient India and aim to control (yoke) and still the mind, recognizing a detached witness-consciou ...

herbal medicine Herbal medicine (also herbalism) is the study of pharmacognosy and the use of medicinal plants, which are a basis of traditional medicine. With worldwide research into pharmacology, some herbal medicines have been translated into modern remed ...

(including the use of

medical cannabis Medical cannabis, or medical marijuana (MMJ), is cannabis and cannabinoids that are prescribed by physicians for their patients. The use of cannabis as medicine has not been rigorously tested due to production and governmental restrictions ...

hyperbaric oxygenation Hyperbaric medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric oxygen therapy (HBOT), the medical use of oxygen at an ambient pressure ...

, self-infection with

hookworm Hookworms are intestinal, blood-feeding, parasitic roundworms that cause types of infection known as helminthiases. Hookworm infection is found in many parts of the world, and is common in areas with poor access to adequate water, sanitation, an ...

(known generally as

helminthic therapy Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the eggs of a helminth. Helminths are parasitic worms such as hoo ...

) and bee venom therapy,

reflexology Reflexology, also known as zone therapy, is an alternative medical practice involving the application of pressure to specific points on the feet, ears, and hands. This is done using thumb, finger, and hand massage techniques without the use of ...

acupuncture Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientifi ...

. Regarding the characteristics of users, they are more frequently women, have had MS for a longer time and tend to be more disabled. Moreover, they also have lower levels of satisfaction with conventional healthcare.

Acute attacks

Disease-modifying treatments

Medications

Side effects

Clinically isolated syndrome

Relapsing-remitting MS

Secondary progressive MS and progressive relapsing MS

Primary progressive MS

Managing the effects of MS

Rehabilitation

Physical therapy

Neurorehabilitation

Medical treatments for symptoms

Research

Stem cell transplant

CCSVI

Alternative treatments

References

Further reading