Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the immune system attacks the central nervous system (CNS), leading to demyelination. It may cause numerous physical and mental symptoms, and often progresses to physical and cognitive disability. Disease onset usually occurs in young adults, and it is more common in women. It has a prevalence that ranges between 2 and 150 per 100,000 depending on the country or specific population. MS was first described in 1868 by Jean-Martin Charcot.
MS affects the areas of the brain and spinal cord known as the white matter. White matter cells carry signals between the grey matter areas, where the processing is done, and the rest of the body. More specifically, MS destroys oligodendrocytes which are the cells responsible for creating and maintaining a fatty layer, known as the myelin sheath, which helps the neurons carry electrical signals. MS results in a thinning or complete loss of myelin and, less frequently, the cutting (transection) of the neuron's extensions or axons. When the myelin is lost, the neurons can no longer effectively conduct their electrical signals. The name multiple sclerosis refers to the scars (scleroses - better known as plaques or lesions) in the white matter. Loss of myelin in these lesions causes some of the symptoms, which vary widely depending upon which signals are interrupted. However, more advanced forms of imaging are now showing that much of the damage happens outside these regions. Almost any neurological symptom can accompany the disease.
MS takes several forms, with new symptoms occurring either in discrete attacks (relapsing forms) or slowly accumulating over time (progressive forms). Most people are first diagnosed with relapsing-remitting MS but develop secondary-progressive MS (SPMS) after a number of years. Between attacks, symptoms may go away completely, but permanent neurological problems often persist, especially as the disease advances.
Although much is known about the mechanisms involved in the disease process, the cause remains elusive: the most widely-held theory being that the condition results from attacks to the nervous system by the body's own immune system. Some believe it is a metabolically dependent disease while others think that it might be caused by a virus such as Epstein-Barr. Still others believe that its virtual absence from tropical areas points to a deficiency of vitamin D during childhood.
This disease does not have a cure, but several therapies have proven helpful. Treatments attempt to return function after an attack, prevent new attacks, and prevent disability. MS medications can have adverse effects or be poorly tolerated, and many patients pursue alternative treatments, despite the paucity of supporting scientific study. Many candidate therapies are still under investigation.
The prognosis, or expected course of the disease, depends on the subtype of the disease, the individual patient's disease characteristics, the initial symptoms, and the degree of disability the person experiences as time advances. Life expectancy of patients, however, is nearly the same as that of the unaffected population, and in some cases a near-normal life is possible.
Signs and symptoms
Symptoms of MS usually appear in episodic acute periods of worsening (relapses, exacerbations, bouts or attacks), in a gradually-progressive deterioration of neurologic function, or in a combination of both.
The most common presentation of MS is the clinically isolated syndrome (CIS). In CIS, a patient has an attack suggestive of demyelination, but he does not fulfill the criteria for multiple sclerosis. In fact, only 30 to 70% of persons experiencing CIS later develop MS. The disease usually presents with sensorial (46% of cases), visual (33%), cerebellar (30%) and motor (26%) symptoms. Many rare initial symptoms have also been reported. These include, but may not be limited to, aphasia, psychosis or epilepsy. Patients first seeking medical attention commonly present with multiple symptoms. The initial signs and symptoms of MS are often transient, mild, and self-limited. These signs and symptoms often do not prompt a person to seek medical attention and are sometimes identified only retrospectively once the diagnosis of MS has been made. Cases of MS are sometimes incidentally identified during neurological examinations performed for other causes. Such cases are referred to as subclinical MS.
The person with MS can suffer almost any neurological symptom or sign, including changes in sensation (hypoesthesias and paraesthesias), muscle weakness, muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, or diplopia), fatigue and acute or chronic pain, and bladder and bowel difficulties. Cognitive impairment of varying degrees and emotional symptomatology in the form of depression or labile affect are also common. The main clinical measure of disability progression and symptom severity is the Expanded Disability Status Scale or EDSS.
Multiple sclerosis relapses are often unpredictable, occurring without warning and without obvious inciting factors. Some attacks, however, are preceded by common triggers. Relapses occur more frequently during spring and summer. Infections such as the common cold, influenza, or gastroenteritis increase the risk of relapse. Stress may also trigger an attack. Pregnancy may affect susceptibility to relapse, offering protection during the last trimester, for instance. During the first few months after delivery, however, the risk of relapse is increased. Overall, pregnancy does not seem to influence long-term disability. Many potential triggers have been examined and found not to influence MS relapse rates. There is no evidence that vaccination for influenza, hepatitis B, varicella, tetanus, or tuberculosis increases risk of relapse. Trauma does not trigger relapses. Exposure to higher than usual ambient temperatures can exacerbate extant symptoms, an effect known as Uhthoff's phenomenon. Uhthoff's phenomenon is not, however, an established relapse trigger.
Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis but also for therapeutic decisions. In 1996 the United States National Multiple Sclerosis Society standardized four subtype definitions; relapsing remitting, secondary progressive, primary progressive and progressive relapsing.
Relapsing-remitting This subtype is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits suffered during the attacks may either resolve or leave sequelae. It describes the initial course of 85 -90% of individuals with MS. When deficits always resolve between attacks, this is sometimes referred to as benign MS.
Secondary progressive describes those with initial relapsing-remitting MS, who then begin to have progressive neurologic decline between their acute attacks without any definite periods of remission. Occasional relapses and minor remissions may appear. The median time between disease onset and conversion from relapsing remitting to secondary progressive is 19 years.
Primary progressive describes the approximately 10-15% of individuals who never have remission after their initial MS symptoms. It is characterized by disease showing progression of disability from onset, without or only occasional and minor remissions and improvements, Age of onset is later than other subtypes.
Progressive relapsing describes those individuals who, from the onset of their MS, have a steady neurologic decline but also suffer clear superimposed attacks; and is the least common of all subtypes.
Special cases of the disease with non-standard behavior have also been described. These cases are Devic's disease, Balo concentric sclerosis, Schilder's diffuse sclerosis and Marburg multiple sclerosis, and are sometimes referred to as borderline forms of multiple sclerosis. There is debate whether they represent MS atypical variants or different diseases.
Multiple sclerosis can be difficult to diagnose since its signs and symptoms may be similar to many other medical problems. Medical organizations have created diagnostic criteria to ease and standardize the diagnostic process for practicing physicians. Historically, different criteria were used and the Schumacher and Poser criteria were both popular. Currently, the McDonald criteria focus on a demonstration with clinical, laboratory and radiologic data of the dissemination of MS lesions in time and space. A diagnosis cannot be made until other possible conditions have been ruled out and there is evidence of demyelinating events separated anatomically and in time.
Clinical data alone may be sufficient for a diagnosis of MS if an individual has suffered separate episodes of neurologic symptoms characteristic of MS. Since some people seek medical attention after only one attack, other testing may hasten and ease the diagnosis. Most commonly used diagnostic tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentials. Magnetic resonance imaging of the brain and spine shows areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously as a contrast to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation. Testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation of the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands, which are an inflammation marker found in 75% to 85% of people with MS. The nervous system of a person with MS often responds less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual and sensory evoked potentials.
MS as an autoimmunological disease
MS is currently believed to be an immune-mediated disorder with an initial trigger, which may have a viral etiology, although this concept has been debated for years and some still oppose it. Considering MS as an autoimmune disease means that damage is believed to be caused by the own immune system of the person with the disease. The immune system of the host attacks the nervous system possibly as a result of exposure to a molecule with a similar structure to its owns.
The name multiple sclerosis refers to the scars (scleroses - better known as plaques or lesions) in the nervous system of those who suffer the disease. MS lesions most commonly involve white matter areas close to the ventricles of the cerebellum, brain stem, basal ganglia, and spinal cord; and the optic nerve. The function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of the body. The peripheral nervous system is rarely involved.
More specifically, MS destroys oligodendrocytes which are the cells responsible for creating and maintaining a fatty layer, known as the myelin sheath, which helps the neurons carry electrical signals. MS results in a thinning or complete loss of myelin and, as the disease advances, the cutting (transection) of the neuron's extensions or axons. When the myelin is lost, neurons can no longer effectively conduct their electrical signals. It is known that a repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes cannot completely rebuild the cells myelin sheath. Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons. Four different lesion patterns have been described.
Apart from demyelination the other pathologic hallmark of the disease is inflammation. According to a strictly immunological explanation of MS, the inflammatory process is caused by T cells, a kind of lymphocytes. Lymphocytes are cells that play an important role in the body's defenses. In MS T cells gain entry into the brain via the blood-brain barrier, a capillary system that should prevent entrance of T-cells into the nervous system. The blood brain barrier is normally not permeable to these types of cells, unless triggered by either infection or a virus, where the integrity of the tight junctions forming the blood-brain barrier is decreased. When the blood brain barrier regains its integrity, usually after infection or virus has cleared, the T cells are trapped inside the brain. These lymphocytes recognize myelin as foreign and attack it as if it were an invading virus. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Leaks form in the blood-brain barrier, which in turn cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins.
Two main measures are used in epidemiological studies: incidence and prevalence. Incidence is the number of new cases per unit of person-time at risk (usually number of new cases per thousand person-years); while prevalence is the total number of cases of the disease in the population at a given time. Prevalence is known to depend not only to incidence, but also to survival rate and migrations of affected people.
Studies on populational and geographical patterns of epidemiological measures have been very common in MS, and have led to the proposal of different etiological (causal) theories.
Regarding age MS usually appears in adults in their thirties. It can also appear in children, and the primary progressive subtype is more common in people in their fifties. As observed in many autoimmune disorders the disease is more common in women and the trend may be increasing. In children the sex ratio may reach three females for each male. In people over fifty, MS affects males and females almost equally.
There is a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere, with MS being much less common in people living near the equator. Climate, sunlight or intake of vitamin D have been investigated as possible causes of the disease that could explain this latitude gradient. However there are important exceptions in the north-south pattern as the Canary islands, prevalence rates change over time, and in general this trend might be dissapearing. All this indicates that other factors such as other environmental factors or genetics have to be taken into account to explain the origin of MS.
Environmental factors during childhood may play an important role in the development of MS later in life. This idea is based on several studies of migrants showing that if migration occurs before the age of fifteen, the migrant acquires the new region's susceptibility to MS. If migration takes place after age fifteen, the migrant keeps the susceptibility of his home country. although the age/geographical risk for developing multiple sclerosis may span a larger timescale.
Regarding genetic factors there is a risk linked to ethnicity being some groups in lower danger of developing the disease even in areas where it is common including the Samis, Turkmen, Amerindians, Canadian Hutterites, Africans, and New Zealand Maoris. Scotland appears to have one the highest rate of MS in the world.
MS epidemiological studies have provided hints on possible causes for the disease. Various theories try to combine the known data into plausible explanations, however none has proved definitive. MS likely occurs as a result of some combination of both environmental and genetic factors.
Genetic causehereditary disease. However genetics may play a role in determining a person's susceptibility to MS.
The risk of acquiring MS is higher in familiars of a person with the disease than in the population, specially in the case of siblings, parents, and children. In the case of monozygotic twins concordance occurs only in about 35% of cases, and half siblings have a lower risk than full siblings indicating a polygenic origin.
Apart from familial studies, specific genes have been linked with MS. There is a group of genes in chromosome 6, the human leukocyte antigen system (HLA) corresponding to the major histocompatibility complex of humans. Changes in this area increase the probability of suffering MS. Two other genes have been clearly related with MS. These are the IL2RA and the IL7RA, subunits of the receptor for interleukin 2 and interleukin 7 respectively. The HLA complex is related to the functioning of the immune system while mutations in the IL2 and IL7 genes were already known to be associated with diabetes and other autoimmune conditions, supporting the notion that MS is an autoimmune disease. Other studies have linked genes in chromosome 5 with the disease.
Genetic susceptibility can explain some some of the geographic and epidemiological variations in MS incidence like the high appearance of the disease among some families or the risk decline with genetic distance but is impossible to account for other phenomena such as the changes in risk that occur with migration at an early age.
An explanation for this epidemiology findings could be that some kind of infection, produced by a widespread microbe rather than a rare pathogen, is in the origin of the disease. Different hypothesis have been elaborated on the mechanism of how this occurs. The hygiene hypothesis proposes that exposure to several infectious agents early in life is protective against MS, similarly to the poliomyelitis model. MS would be an autoimmune reaction triggered in susceptible individuals by multiple infective microorganisms, with risk increasing with age at infection. The prevalence hypothesis proposes that the disease is due to a pathogen more common in regions of high MS prevalence. This pathogen is very common, causing in most individuals an asymptomatic persistent infection. Only in a few cases, and after many years since the original infection it brings demyielination. The hygiene hypothesis has received more support than the prevalence hypothesis.
Evidence of viruses as a cause include the fact that most patients have oligoclonal bands in the brain and cerebrospinal fluid, the association of several viruses with human demyelinating encephalomyelitis, and the possibility of inducing demyelination in animals through viral infection. Human herpesviruses are a candidate group of viruses linked to MS; Varicella zoster virus has been found at high levels in the cerebrospinal fluid of MS patients, but the most reproduced finding is the reduced risk of having the disease in those who have never been infected by the Epstein-Barr virus. This fact goes against the hygiene hypothesis since non-infected have probably experienced a more hygienic upbringing. Other agents that have also been related with MS are human endogenous retroviruses and chlamydia pneumoniae.
Non infectious environmental risk factors
MS seems to be more common in people who live farther from the equator. Decreased sunlight exposure has been linked with a higher risk of MS. Decreased vitamin D production and intake has been the main biological mechanism used to explain the higher risk among those less exposed to sun.
Severe stress may also be a risk factor although evidences are weak; parents who have lost a child unexpectedly are more likely to develop MS than parents who had not. Smoking has also been shown to be an independent risk factor for developing MS. Association with occupational exposures and toxins; mainly solvents; has been evaluated but no clear conclusions have been reached. Vaccinations were also considered as causal factors for the disease; however most studies are consistent in showing no association between MS and vaccines.
Gout occurs less than would statistically be expected in people with MS, and low levels of uric acid have been found in MS patients as compared to normal individuals. This led to the theory that uric acid, which can protect against oxidative stress from substances such as peroxynitrite, protects against MS, although its exact importance remains unknown. Several other possible risk factors such as diet or hormones intake have been investigated however more evidences are needed to confirm or disconfirm their relation with the disease.
Although some of this risk factors, including infection, are partly modifiable only further research, and specially clinical trials, will reveal whether, in fact, their elimination can help to prevent MS.
Although there is no known cure for multiple sclerosis, several therapies have proven helpful. 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 have several adverse effects. At the same time different alternative treatments are pursued by some patients, despite the paucity of supporting, comparable, replicated scientific study.
Management of acute attacks
During symptomatic attacks administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the routine therapy for acute relapses. The aim of this kind of treatment is to end the attack sooner and leave fewer lasting deficits in the patient. Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery. Potential side effects include osteoporosis and impaired memory, the latter being reversible.
Disease modifying treatments
As of 2007, six disease-modifying treatments have been approved by regulatory agencies of different countries for relapsing-remitting MS. Three are interferons: two formulations of interferon beta-1a (trade names Avonex and Rebif) and one of interferon beta-1b (U.S. trade name Betaseron, in Europe and Japan Betaferon). A fourth medication is glatiramer acetate (Copaxone). The fifth medication, mitoxantrone, is an immunosuppressant also used in cancer chemotherapy, is approved only in the USA and largely for SPMS. Finally, the sixth is natalizumab (marketed as Tysabri). All six medications are modestly effective at decreasing the number of attacks and slowing progression to disability, although they differ in their efficacy rate and studies of their long-term effects are still lacking. Comparisons between immunomodulators (all but mitoxantrone) show that the most effective is natalizumab, both in terms of relapse rate reduction and halting disability progression; it has also been shown to reduce the severity of MS.
Mitoxantrone may be the most effective of them all; however, it is generally considered not as a long-term therapy as its use is limited by severe cardiotoxicity.
The interferons and glatiramer acetate are delivered by frequent injections, varying from once-per-day for glatiramer acetate to once-per-week (but intra-muscular) for Avonex. Natalizumab and mitoxantrone are given by IV infusion at monthly intervals.
Treatment of progressive MS is more difficult than relapsing-remitting MS. Mitoxantrone has shown positive effects in patients 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 patients in short-term follow-up. On the other hand no treatment has been proven to modify the course of primary progressive MS.
As with any medical treatment, these treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the Interferon treatments. Over time, a visible dent at the injection site due to the local destruction of fat tissue, known as lipoatrophy, may develop. Interferons also produce symptoms similar to influenza; while some patients taking glatiramer experience a post-injection reaction manifested by flushing, chest tightness, heart palpitations, breathlessness, and anxiety, which usually lasts less than thirty minutes. More dangerous are liver damage of interferons and mitoxantrone, the immunosuppressive effects and cardiac toxicity of the latter; or the putative link between natalizumab and some cases of progressive multifocal leukoencephalopathy.
Management of the effects of MS
Disease-modifying treatments only reduce the progression rate of the disease but do not stop it. As multiple sclerosis progresses, the symptomatology tends to increase. The disease is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and handicap. Management of these deficits is therefore very important. Both drug therapy and neurorehabilitation have shown to ease the burden of some symptoms, even though neither influence disease progression.
As for any patient with neurologic deficits, a multidisciplinary 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. Similarly for each symptom there are different treatment options. Treatments should therefore be individualized depending both on the patient and the physician
As with most chronic diseases, alternative treatments are pursued by some patients, despite the shortage of supporting, comparable, replicated scientific study. Examples are dietary regimens, herbal medicine, including the use of medical cannabis to help alleviate symptoms, or hyperbaric oxygenation.
The prognosis (the expected future course of the disease) for a person with multiple sclerosis depends on the subtype of the disease; the individual's sex, race, age, and initial symptoms; and the degree of disability the person experiences. The life expectancy of people with MS, at least for earlier years, is now nearly the same as that of unaffected people. This is due mainly to improved methods of limiting disability, such as physical therapy, occupational therapy and speech therapy, along with more successful treatment of common complications of disability, such as pneumonia and urinary tract infections. Nevertheless, half of the deaths in people with MS are directly related to the consequences of the disease, while 15% more are due to suicide.
- Individuals with progressive subtypes of MS, particularly the primary progressive subtype, have a more rapid decline in function. In the primary progressive subtype, supportive equipment (such as a wheelchair or standing frame) is often needed after six to seven years. However, when the initial disease course is the relapsing-remitting subtype, the average time until such equipment is needed is twenty years. This means that many individuals with MS will never need a wheelchair. There is also more cognitive impairment in the progressive forms than in the relapsing-remitting course.
- The earlier in life MS occurs, the slower disability progresses. Individuals who are older than fifty when diagnosed are more likely to experience a chronic progressive course, with more rapid progression of disability. Those diagnosed before age 35 have the best prognosis. Females generally have a better prognosis than males. Although individuals of African descent tend to develop MS less frequently, they are often older at the time of onset and may have a worse prognosis.
- Initial MS symptoms of visual loss or sensory problems, such as numbness or tingling, are markers for a relatively good prognosis, whereas difficulty walking and weakness are markers for a relatively poor prognosis. Better outcomes are also associated with the presence of only a single symptom at onset, the rapid development of initial symptoms, and the rapid regression of initial symptoms.
- The degree of disability varies among individuals with MS. In general, one of three individuals will still be able to work after 15–20 years. Fifteen percent of people diagnosed with MS never have a second relapse, and these people have minimal or no disability after ten years. The degree of disability after five years correlates well with the degree of disability after fifteen years. This means that two-thirds of people with MS with low disability after five years will not get much worse during the next ten years. It should be noted that most of these outcomes were observed before the use of medications such as interferon, which can delay disease progression for several years.
- Apart from physical disability, cognitive impairment in MS occurs in approximately half of all patients. In its earlier stages, this impairment can include loss of short-term memory, depression and the pseudobulbar affect. As the disease progresess, the impairment can become more profound, ranging from loss of deductive reasoning to dementia.
Currently there are no clinically established laboratory investigations available that can predict prognosis or response to treatment. However, several promising approaches have been proposed. These include measurement of the two antibodies anti-myelin oligodendrocyte glycoprotein and anti-myelin basic protein, measurement of TRAIL (TNF-related apoptosis-inducing ligand)., and recently, lipid-specific immunoglobulin M in CSF as predictor of the long time behavior.
The French neurologist Jean-Martin Charcot (1825–1893) was the first person to recognize multiple sclerosis as a distinct disease in 1868. Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of MS now known as Charcot's triad 1 are nystagmus, intention tremor and telegraphic speech, though does not only appear in MS. Charcot also observed cognition changes since he described his patients as having a "marked enfeeblement of the memory" and "with conceptions that formed slowly".
Prior to Charcot, Robert Hooper (1773–1835), a British pathologist and practicing physician, Robert Carswell (1793–1857), a British professor of pathology, and Jean Cruveilhier (1791–1873), a French professor of pathologic anatomy, had described and illustrated many of the disease's clinical details, but did not identify it as a separate disease.
There are several historical accounts of people who lived before or shortly after the disease was described by Charcot but probably had MS.
A young woman called Halldora, who lived in Iceland around the year 1200, suddenly lost her vision and mobility; but after praying to the saints recovered them seven days after. Saint Lidwina of Schiedam (1380–1433), a Dutch nun, may be one of the first clearly identifiable MS patients. From the age of sixteen until her death at age 53, she suffered intermittent pain, weakness of the legs, and vision loss—symptoms typical of MS. Both cases have led to the proposal of a 'viking gene' hypothesis for the dissemination of the disease.
Augustus Frederick d'Este (1794–1848), an illegitimate grandson of King George III of Great Britain, almost certainly suffered from MS. D'Este left a detailed diary describing his 22 years living with the disease. He began his diary in 1822 and it had its last entry in 1846 (only to remain unknown until 1948). His symptoms began at age 28 with a sudden transient visual loss after the funeral of a friend. During the course of his disease he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life.
Another early account of MS was kept by the British diarist W. N. P. Barbellion, nom-de-plume of Bruce Frederick Cummings (1889–1919), who maintained a detailed log of his diagnosis and struggle with MS. His diary was published in 1919 as The Journal of a Disappointed Man.
Scientists continue their extensive efforts to create new and better therapies for MS. There are a number of treatments under investigation that may curtail attacks or improve function. Some of these treatments involve the combination of drugs that are already in use for multiple sclerosis, such as the joint administration of mitoxantrone and glatiramer acetate (Copaxone). However most treatments already in clinical trials involve drugs that are used in other diseases. These are the cases of alemtuzumab (trade name Campath), daclizumab (trade name Zenapax), inosine, or BG00012. Other drugs in clinical trials have been designed specifically for MS, such as fingolimod, laquinimod, or Neurovax.
Low dose naltrexone has been prescribed off-label for certain autoimmune disorders, including MS, and there is anecdotal evidence of benefit, but only a small clinical trial for the primary progressive variety has been published.
New diagnostic and evolution evaluation methods are also being investigated. The measurement of antibodies against myelin proteins such as myelin oligodendrocyte glycoprotein and myelin basic protein could be useful for diagnosis. Optical coherence tomography of the eye's retina could be used as a measure of response to medication, axonal degeneration and brain atrophy.
Finally, there are also many early-stage investigations that in the future may emerge as new treatments. Examples of these are the studies trying to understand the influence of Chlamydophila pneumoniae or vitamin D in the origin of the disease, or preliminary investigations on the use of helminthic therapy.
- Langgartner M, Langgartner I, Drlicek M. The patient's journey: multiple sclerosis. BMJ. 2005 Apr 16;330(7496):885-8. PMID 15831874.
- Database for analysis and comparison of global data on the epidemiology of MS
- NIH listing of clinical trials related to MS
- Abstract index of the Cochrane Library