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[[Herbal medicine]] is another source for alternative treatments. [[Andrographis paniculata]], [[Glycyrrhiza uralensis]] and [[Forsythia suspensa]]; 3 medicinal plants traditionally used in China for treating conditions associated with inflammation and viral infection reduced the inflammation of [[epithelial]] cells infected by [[influenza A]] virus. Since inflammation is crucial in MS in the future these plants could be utilized to ease the progression of the disease.<ref name="pmid16621378">{{cite journal |author=Ko HC, Wei BL, Chiou WF |title=The effect of medicinal plants used in Chinese folk medicine on RANTES secretion by virus-infected human epithelial cells |journal=Journal of ethnopharmacology |volume=107 |issue=2 |pages=205-10 |year=2006 |pmid=16621378 |doi=10.1016/j.jep.2006.03.004}}</ref> Many patients also use medical [[marijuana]] to help alleviate symptoms; however, the results of experimental studies are scarce; but at least a subgroup with greater disability appears to derive some symptomatic benefit<ref>{{cite journal |author=Chong MS, Wolff K, Wise K, Tanton C, Winstock A, Silber E |title=Cannabis use in patients with multiple sclerosis |journal=Mult. Scler. |volume=12 |issue=5 |pages=646-51 |year=2006 |pmid=17086912 |doi=}}</ref><ref>{{cite journal |author=Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, Nunn AJ, Teare LJ, Fox PJ, Thompson AJ |title=Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up |journal=J. Neurol. Neurosurg. Psychiatr. |volume=76 |issue=12 |pages=1664-9 |year=2005 |pmid=16291891 |doi=10.1136/jnnp.2005.070136}}</ref>
[[Herbal medicine]] is another source for alternative treatments. [[Andrographis paniculata]], [[Glycyrrhiza uralensis]] and [[Forsythia suspensa]]; 3 medicinal plants traditionally used in China for treating conditions associated with inflammation and viral infection reduced the inflammation of [[epithelial]] cells infected by [[influenza A]] virus. Since inflammation is crucial in MS in the future these plants could be utilized to ease the progression of the disease.<ref name="pmid16621378">{{cite journal |author=Ko HC, Wei BL, Chiou WF |title=The effect of medicinal plants used in Chinese folk medicine on RANTES secretion by virus-infected human epithelial cells |journal=Journal of ethnopharmacology |volume=107 |issue=2 |pages=205-10 |year=2006 |pmid=16621378 |doi=10.1016/j.jep.2006.03.004}}</ref> Many patients also use medical [[marijuana]] to help alleviate symptoms; however, the results of experimental studies are scarce; but at least a subgroup with greater disability appears to derive some symptomatic benefit<ref>{{cite journal |author=Chong MS, Wolff K, Wise K, Tanton C, Winstock A, Silber E |title=Cannabis use in patients with multiple sclerosis |journal=Mult. Scler. |volume=12 |issue=5 |pages=646-51 |year=2006 |pmid=17086912 |doi=}}</ref><ref>{{cite journal |author=Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, Nunn AJ, Teare LJ, Fox PJ, Thompson AJ |title=Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up |journal=J. Neurol. Neurosurg. Psychiatr. |volume=76 |issue=12 |pages=1664-9 |year=2005 |pmid=16291891 |doi=10.1136/jnnp.2005.070136}}</ref>

[[Hyperbaric oxygenation]] has been the subject of several small studies with heterogeneous results which, overall, do not support its use.<ref name="pmid14974004">{{cite journal |author=Bennett M, Heard R |title=Hyperbaric oxygen therapy for multiple sclerosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD003057 |year=2004 |pmid=14974004 |doi=10.1002/14651858.CD003057.pub2}}</ref>


==References==
==References==

Revision as of 07:51, 15 August 2007

There is no known definitive cure for multiple sclerosis (MS). However, several types of therapy have proven to be helpful. 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. Treatment is aimed at returning function after an attack, preventing new attacks, and preventing disability.

Main alternative treatmentsinvolve nutritional supplements, and/or dietary measures, however many non scientifically proved treatments are trie by the patients: some patients may adhere to mainstream pharmaceutical treatment options while others may also choose to apply a form of precautionary principle, where potentially helpful and/or preventive measures are employed despite a paucity of supporting, comparable, replicated scientific study.

This article focuses only in therapies for standard MS. The borderline forms of MS (Balo concentric sclerosis, Marburg multiple sclerosis, Schilder's disease, Devic's disease and acute disseminated encephalomyelitis) are explicitly excluded, as they have their own particular treatments.

Management of acute attacks

During symptomatic attacks, patients may be hospitalized. High doses of intravenous corticosteroids, such as methylprednisolone,[1][2] is the routine therapy for acute relapses at present. These are given over a period of 3 to 5 days; having a well stablished efficacy promoting a better recovery of disability as measured by the Expanded Disability Status Scale score (EDSS).[3][4]

The aim of this kind of treatment is to end the attack sooner and leave fewer lasting deficits. Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery: corticosteroids produce a rapid improvement in disability; but this improvement only lasts up to 30 days following the clinical attack, is neither evident 6 or 36 months after the atack, and does not reduce the number of patients who would subsequently develop a clinical relapse.[5]

Recent studies suggest that oral steroid pills are just as effective at treating MS symptoms as intravenous treatment. However short term treatment with high dose intravenous corticosteroids does not seem to be attended by adverse effects. On the contrary, gastrointestinal symptoms and psychic disorders are more common with oral corticosteroids.[6]

Management of relapsing-remitting MS

In the United States, as of 2006 there are six Food and Drug Administration (FDA)-approved treatments for patients with relapsing-remitting MS. Three are interferons: Interferon beta-1a, (Avonex and Rebif) [7] [8] or beta-1b (Betaseron [in Europe and Japan Betaferon]).[9] The interferons are medications derived from human cytokines which help regulate the immune system. A fourth medication is glatiramer acetate (Copaxone),[10] a mixture of polypeptides which may protect important myelin proteins by substituting itself as the target of immune system attack. The fifth medication, mitoxantrone, is probably the most effective of them all[11] but is limited by cardiac toxicity. Finally, the sixth medication is Natalizumab (marketed as Tysabri).[12] Natalizumab was finally approved in May 2006 after a long process, due to cases of progressive multifocal leukoencephalopathy (PML) in some patients who had taken it in combination with interferons.

All six medications have been proven to be modestly effective at decreasing the number of attacks and slowing progression to disability. They differ primarily in ease of use, price, side effects, and the likelihood that extended use will decrease their effects. All these therapies are expensive and require frequent injections, with Tysabri is given as intravenous infusions every four weeks, Avonex requiring weekly injections and Copaxone daily injections. All of the interferons can lose effectiveness after continued use, with Avonex being the least likely and Betaseron the most likely. This is the result of neutralizing antibodies against the interferons. The interferons all require laboratory monitoring of blood tests. Even with appropriate use of medication, most patients with relapsing-remitting MS still suffer from some attacks and subsequent disability. Side effects are covered below.

Side effects of medications for relapsing-remitting MS

The two most common types of medications used to treat relapsing-remitting MS have significant side effects which warrant further discussion. Both the interferons and glatiramer acetate are available only in injectable forms, and both can cause irritation at the injection site. Interferons are produced in the body during illnesses such as influenza in order to help fight the infection. They are responsible for the fever, muscle aches, fatigue, and headache common during influenza infections. Many patients report influenza-like symptoms when using interferon to fight MS. This reaction often lessens over time and can be treated with over-the-counter fever reducers/pain relievers like paracetamol (acetaminophen), ibuprofen, and naproxen. Many patients choose not to take interferon due to the unpleasant experience of frequent injections and their subsequent side effects, citing a loss in their quality of life. Neurologists advocating for the use of these medications in modifying the progression of disease believe the long term benefits outweigh the short-term side effects. Interferons can cause liver damage, and laboratory blood tests must be monitored to ensure safe use. Some patients taking glatiramer acetate experience a "post-injection" reaction manifested by flushing, chest tightness, heart palpitations, breathlessness, and anxiety.

Management of progressive MS

Treatment of progressive MS is more difficult than relapsing-remitting MS, and many patients do not respond to any therapy. A wide range of medications have been used to try to slow the progression of disease. Many therapies have been shown to have some effect on disease progression and resulting disability, but most therapies have significant side effects which limit their long-term use. Therefore they are often appropriate only for the most rapidly progressive cases. Azathioprine, cladribine, and ciclosporin have all shown small benefits, which in most cases are outweighed by side effects such as an increased cancer risk. Bone marrow transplant, plasmapheresis, and total lymphoid irradiation (exposure to high doses of radiation in order to kill parts of the immune system) have been studied and are currently reserved for the most dire cases. Cyclophosphamide and methotrexate are chemotherapy drugs which can slow the progression of MS, but which also have a number of side effects. Frequent courses of high-dose corticosteroids, often given weekly or monthly, are also commonly employed to good effect.

Specific for secondary progressive

Interferons show promise in secondary progressive MS, but more data is needed to support widespread use.[citation needed] Mitoxantrone, a chemotherapy drug, has been approved for secondary progressive, and offers a significant reduction in progression to disability, but causes dose-dependent cardiac toxicity which limits its long-term use.[citation needed]

Management of demyelination without a diagnosis of MS

Several studies have shown that starting treatment with interferon beta-1a during the initial attack (and prior to the second attack required for a definite diagnosis of MS) can decrease the chance that a patient will develop MS. A separate medication, intravenous immunoglobulin (IVIG) has also shown promise in reducing progression to MS in this set of patients. Therefore, in certain patients, it is important that therapy be started prior to definite diagnosis.[13][14]

Management of the effects of MS

Because much of the damage caused by MS is irreversible, management of the resulting deficits is very important.

A multidisciplinary approach

As for any patient with neurologic deficits, a multidisciplinary approach is key to limiting and overcoming disability. Physical therapy, occupational therapy, and supportive equipment such as wheelchairs and standing frames may be helpful. Speech therapy can help maintain quality of life. Treatment of emotional distress and depression should involve mental health professionals such as therapists, psychologists, and psychiatrists. Neuropsychologists can help to evaluate and manage cognitve deficits.

Management of cognitive deficits

Neurocognitive testing is important for determining the extent of cognitive deficits. Neuropsychological stimulation may help to reverse or decrease the cognitive defects although its management relies on lifestyle strategies.

Interferons have demonstrated that can help to reduce cognitive limitations in multiple sclerosis.[15]

Anticholinesterase drugs such as donepezil commonly used in alzheimer disease; although not approved yet for multiple sclerosis; have also shown efficacy in different clinical trials.[16][17]

Medications for different symptoms

Medications such as baclofen, tizanidine, dantrolene and Sativex have been shown to improve spasticity. Depression can be treated with a variety of antidepressants; selective serotonin reuptake inhibitors (SSRIs) are most commonly employed. The anticonvulsant drugs gabapentin and carbamazepine and the antidepressant amitriptyline can improve pain and tingling sensations in certain cases. Fatigue can often be managed by amantadine, pemoline, methylphenidate, and modafinil. Bladder spasms can be treated by oxybutynin and trospium chloride. Erectile dysfunction may respond to sildenafil, vardenafil, or tadalafil. Different drugs as well as optic compensatory systems and prisms can be used to improve the symptoms of nystagmus.;[18][19][20][21] Surgery can also be used in some cases for this problem.[22] Testosterone has been studied for its potential benefits in men with Multiple Sclerosis, but the results are preliminary. Template:Sicotte et. al. Testosterone Treatment in Multiple Sclerosis. Arch Neurol, vol.64, may 2007, p.683-8

Medications for pain

Sativex, call "The Spray" by users, is approved in Canada, UK, and Spain for treatment to relieve pain in multiple sclerosis patients. Due to its use of cannabis it is currently not available in the US, but is undergoing Phase III testing right now for approval. In the US patients can apply for Sativex under the Compassionate Use program.[23]

Other treatments

Electrical stimulation underneath the skin, (electroacupuncture), can relieve bladder problems caused by multiple sclerosis.[24]

Therapies under investigation

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, both for new drugs and for combinations of them.

Combination of approved drugs

  • A recent study in the United Kingdom revealed promising results when using a combination of mitoxantrone (an immunosuppressive drug normally used in cancer) and Glatiramer acetate (Copaxone). In an 'open' study of 27 patients with Relapsing Remitting MS, the combination was found to provide a rapid and sustained suppression of relapses in MS patients experiencing frequent, recurrent and disabling attacks (90% reduction in annualised relapse rate maintained, to date, for a mean of 36 months). A three year controlled study is now being launched at 10 centres across the UK.[25].

Disease modifying drugs in phase II and III clinical trials

Drugs aimed to modify the natural course of the disease instead of targeting the sympthoms or the recovery. Over a dozen clinical trials testing potential therapies are underway, and additional new treatments are being devised and tested in animal models.

  • Fingolimod: fingolimod is a sphingosine-1-phosphate receptor modulator. In 2006 it showed promising results in a phase II clinical trial for relapsing multiple sclerosis with a relapse reduction of over 50% compared to placebo and an acceptable safety profile.[28]. Another advantage of this treatment is its oral administration. A phase III trial is ongoing.[29]
  • Neurovax: this medication is a vaccine being tested for use in Multiple Sclerosis. In 2005 it was in phase II clinical trials;[30] but in 2007 no results had been published yet.
  • Inosine: Inosine is a compound that has had good results in phases I and II.[31][32] Two different ways of action have been proposed. First, it produces uric acid after ingestion,[33] which is a natural antioxidant,[34][35] second, it has been shown to induce axonal rewiring and is used as a treatment for stroke,[36] and spinal cord injury</ref>[37] and third, it has shown neuroprotective and anti-inflammatory effects independently of the other two.[38].

Other investigations on possible treatments

  • Statins: a family of cholesterol-lowering drugs, the statins, have shown anti-inflammatory effects in animal models of MS.[39] However, as of 2007 there is not sufficient evidence that statins are beneficial in the treatment of human MS patients.
  • Vitamin D: a 2004 study found that women who took vitamin D supplements were 40% less likely to develop MS than women who did not take supplements. However, this study does not provide enough data to conclude that vitamin D has a beneficial influence on ongoing MS. Furthermore, it could not distinguish between a beneficial effect of vitamin D and that of multivitamin supplements including vitamin E and various B vitamins, which may also exert a protective effect.[40]
  • Antimicrobial agents against Chlamydophila pneumoniae: MS patients are more likely to have detectable levels of Chlamydophila pneumoniae DNA in their cerebrospinal fluid, compared to other patients with neurological diseases; however these findings are insufficient to establish an etiologic relation.[41] Anecdotal reports of the use of antimicrobial agents against Chlamydophila pneumoniae are favorable, but only one double-blind placebo-controlled trial has been published, in which the number of patients studied was too small (four in each arm of the trial) to reach statistical significance in the primary outcome measure (volume of gadolinium-enhancing lesions, as viewed on MRI).[42]
  • Prolactin:In 2007 it was published that the hormone prolactin can ease the effects of dymielination in animal models of MS.[43] This effect of prolactin may be the reason why pregnancy tends to reduce the effects of multiple sclerosis in women.[44]
  • Minocycline: antibiotic mynocline has shown an effect on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in MS patients over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment relapse rate in patients in the study prior to treatment, no relapses occurred between months 6 and 24. The only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Clinical and MRI outcomes in this study were supported by systemic immunological changes and call for further investigation of minocycline in MS.[45]
  • Cyclophosphamide: in a 2006 study cyclophosphamide was given to patients with moderate to severe refractory (They had alredy tried approved medication) multiple sclerosis for four days. These patients were followed for two years. They showed a disease stabilization and improved functionality.[46] However a review of the different studies that investigate if cyclophosphamide is useful for progressive MS does not support its use in clinical practice.[47]
  • Testosterone has been studied for its potential benefits in men with Multiple Sclerosis, but the results are preliminary. [48]
  • A study published in 2007 showed a negative association between multiple sclerosis and infection with intestinal parasites, such as hookworm indicating that parasites may protect against multiple sclerosis.[49]

Alternative treatments

Main article: Dietary treatments for multiple sclerosis

and Endocannabinoid System and Multiple Sclerosis

Clinical and experimental data suggest that certain dietary regimens, particularly those including polyunsaturated fatty acids, and vitamins might improve outcomes in people with multiple sclerosis.[50][51] Many diets have been proposed for treating the symptoms of the disease. Patients have reported a decrease of symptoms after long-term application of the diets; however no controlled trials have been able to proof their efficacy. [52] Even if these diets really are benefitial for people with MS, it is uncertain whether this fact is due to some special traits of the diets or simply that they are beneficial for whole body health. Some examples of these kind of diets are the Swank Multiple Sclerosis Diet or the The Optimal Diet.[53]

Herbal medicine is another source for alternative treatments. Andrographis paniculata, Glycyrrhiza uralensis and Forsythia suspensa; 3 medicinal plants traditionally used in China for treating conditions associated with inflammation and viral infection reduced the inflammation of epithelial cells infected by influenza A virus. Since inflammation is crucial in MS in the future these plants could be utilized to ease the progression of the disease.[54] Many patients also use medical marijuana to help alleviate symptoms; however, the results of experimental studies are scarce; but at least a subgroup with greater disability appears to derive some symptomatic benefit[55][56]

Hyperbaric oxygenation has been the subject of several small studies with heterogeneous results which, overall, do not support its use.[57]

References

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