Introduction:-
Multiple sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the CNS, MS attacks the myelinated axons in the CNS, destroying the myelin and the axons to varying degrees.
The course of MS is highly varied and unpredictable. In most patients, the disease is characterized initially by episodes of reversible neurological deficits, which is often followed by progressive neurological deterioration over time.
From 250.000 to 350,000 patients in the U.S. have MS, and 50% of patients will need help walking within 15 years after the one set of the disease
Multiple sclerosis types:-
The neurologist agree that patients might be grouped into 4 major groups:-
1-Relapsing-remitting MS: the most common form affecting about 85% of MS patients. It is marked by flare-ups (relapses or exacerbations) of symptoms followed by periods of remission, when symptoms improve or disappear.
2-Secondary progressive MS: may develop in some patients with relapsing–remitting disease. For many patients, treatment with disease-modifying agents helps delay such progression. The disease course continues to worsen with or without periods of remission or leveling off of symptom severity (plateaus).
3-Primary progressive MS: affects approximately10% of MS patients. Symptoms continue to worsen gradually from the beginning. There are no relapses or remissions, but there may be occasional plateaus. This form of MS is more resistant to the drugs typically used to treat the disease.
4-Progressive-relapsing MS: a rare form, affecting fewer than 5% of patients. It is progressive from the start, with intermittent flare-ups of worsening symptoms along the way. There are no periods of remission
Diagnosis:-
There is no single diagnostic test for MS. The diagnosis is based on evidence of (1) at least two different lesions (plaques or scars) in the white matter of the CNS (the space dissemination criterion); (2) at least two different episodes in the disease course (the time dissemination criterion); and (3) chronic inflammation of the CNS, as determined by analysis of the CSF(the inflammatory criterion).
The presence of one or more of these criteria allows a general diagnosis of MS, which may be refined according to the subsequent course of the disease. An international panel on the diagnosis of MS suggested that the time dissemination criterion should be confirmed by clinical signs on MRI at least 3 months after the previous clinical episode or on a previous MRI. The panel also suggested that the inflammatory criterion could replace the space dissemination criterion when the latter is missing at the clinical and paraclinical levels.
To make a diagnosis of MS, the physician must:
• find evidence of damage in at least two separate areas of the CNS, which includes the brain, spinal cord, and optic nerves.
• determine that the damaged areas developed at least1 month apart.
• exclude all other possible diagnoses.
• observe that the symptoms last for more than 24 hours and occur as distinct episodes separated by 1 month or more.
• perform an MRI (the most sensitive imaging test for MS)
• perform a spinal tap and examination for oligoclonal bands.
At autopsy, multiple, discrete pink or gray areas that have a hard, rubbery texture are identified within the white matter. The lesions are composed of areas of myelin and oligodendrocyte loss along with infiltrates of inflammatory cells, including lymphocytes and macrophages.The relative preservation of axons and neurons within these lesions helps to differentiate MS from other destructive pathological processes that are accompanied by focal inflammation.
Signs and symptoms:-
More than 30% of MS patients have moderate-tosevere spasticity, mostly in the legs.
Initial clinical findings in MS patients are often sensory disturbances, the most common of which are paresthesias (numbness and tingling), dysesthesias (burning and “pins and needles”), diplopia, ataxia, vertigo, and bladder (urinary sphincter) disturbances. A common manifestation of MS is unilateral numbness affecting one leg that spreads to involve the other leg and rises to the pelvis, abdomen, or thorax. Sensory disturbances usually resolve but sometimes evolve into chronic neuropathic pain. Trigeminal neuralgia also occurs. Another common presenting sign of MS is optic neuritis, highlighted by complete or partial loss of vision. Bladder dysfunction occurs in more than 90% of MS patients and results in weekly or more frequent episodes of incontinence in one-third of patients. At least 30% of patients experience constipation. Fatigue occurs in 90% of patients and is the most common work-related disability associated with MS(1).
Neuropsychiatric signs and symptoms
Neuropsychiatric signs and symptoms occur frequently in individuals with MS, either as the initial presenting complaint prior to a definitive neurological diagnosis or more commonly with disease progression. However, the pathogenesis of these comorbid conditions remains unclear, and it remains difficult to accurately elucidate if neuropsychiatric symptoms or conditions are indicators of MS illness severity. Furthermore, both the disease process and treatments of MS can adversely impact on individual’s mental health. It should also be noted that a significant proportion of MS sufferers do not exhibit neuropsychiatric sequelae. This may be related in part to the ‘theory of resilience,’ where an individual develops an ability to maintain psychological well-being and ability to function in the face of adversity or ‘post-traumatic growth,’ where individuals experience positive psychological changes in response to a challenging situation although of course many very resilient individuals with MS exhibit significant neuropsychiatric sequelae. Optimum treatment of neuropsychiatric symptoms usually requires an interdisciplinary approach, with input from both neurological and psychiatric services. Management strategies include the optimisation of disease-modifying agents, reducing doses of iatrogenic agents where possible, initiating psychotropic agents that are least likely to exacerbate physical symptoms and the addition of appropriate psychotherapeutic interventions.(2)
Euphoria
Euphoria is an abnormal, neurologically based emotional state that is found primarily in patients with advanced, disseminated disease. Its natural history and true prevalence remain unknown. The neuroanatomy is presently presumed to involve extensive bilateral and subfrontal demyelination and scarring that isolate limbic and diencephalic centers from prefrontal modulation. This will require confirmation with magnetic resonance imaging and other scanning techniques.
Pathological laughing and weeping
Pathological laughing and weeping is a neurological syndrome of emotional dyscontrol that is probably caused by disconnection of diencephalic or brain-stem centers from right hemisphere or frontal control. It can be functionally disabling and should be treated either with low-dose amitriptyline or levodopa.
Depression
A number of controlled studies indicate that lifetime prevalence rates for significant depressive illness are higher for patients with MS than for patients with a variety of comparable medical and neurological diseases. The cause of depression remains unclear but is probably due to the interaction of biological, psychological, and social factors. Depressive mood disorders are underrecognized in clinical practice and available therapies are not well used.
Changes in practice patterns detecting depressive illnesses and insuring appropriate psychiatric intervention might make an important contribution to the emotional well being and functional capacity of patients with MS and their families.
Bipolar affictive disorder
Bipolar disorder appears to occur at an unexpectedly high rate among patients with MS. There is preliminary evidence to suggest that this epidemiologically defined association may be based on a biological mechanism, perhaps one involving a shared genetic vulnerability between MS and bipolar disorder.(3)
Treatment
There's no cure for multiple sclerosis sclerosis (MS), but medicines and lifestyle changes can help you manage the disease. Work closely with your doctor to find the treatment that's best for you and causes the fewest side effects.
Disease-Modifying Drugs
If you have a type of multiple sclerosis called relapsing-remitting MS and your condition is acting up, your doctor may first treat you with a disease-modifying drug. These medicines slow down the advance of your disease and prevent flare-ups.
The drugs work by curbing the immune system your body's main defense against germs -- so that it doesn't attack the protective coating called myelin that surrounds the nerves.
Some drugs come as injections under your skin or into a muscle. The shot might make your skin sore, red, itchy, or dimply. They include:
Beta interferons: These are some of the most common drugs used to treat MS. They ease the severity and frequency of flares. They can also cause flu-like symptoms, like aches, fatigue, fever, and chills, but these should fade within a few months. They may make you slightly more likely to get an infection. That’s because they lower the number of white blood cells, which help your immune system fight illnesses. They include:
• Avonex (interferon beta-1a)
• Betaseron (interferon beta-1b)
• Extavia (interferon beta-1b)
• Plegridy (peginterferon beta-1a)
• Rebif (interferon beta-1a)
Glatiramer (Copaxone, Glatopa): This medication stops your immune system from attacking the myelin that surrounds and protects your nerves.
You can take other medications as a pill:
Teriflunomide (Aubagio): is a tablet you take once a day. The most common side effects include diarrhea, abnormal liver tests, nausea, and hair loss. It does carry a "black box" warning, the FDA's most serious warning, because it can lead to liver problems and birth defects. If you take it, your doctor will likely do regular tests to check how well your liver is working. Don’t take it if you're pregnant.
Fingolimod (Gilenya): is also a once-daily tablet. If you haven’t had chickenpox, you’ll need a vaccine. Common side effects include headache, diarrhea, back pain, cough, and abnormal liver tests. Because the medicine may slow your heart rate, the doctor will watch you closely after your first dose. The drug is also linked to progressive multifocal leukoencephalopathy (PML), a rare brain infection.
Dimethyl fumarate (Tecfidera): is a tablet you take twice a day. It can lower your immune cells, so the doctor will do regular blood tests to keep an eye on them. The drug's most common side effects are flushing, stomach pain, diarrhea, nausea, and vomiting. An active ingredient similar to the one in Tecfidera is linked to four cases of PML.
Other medications are given by infusion into a vein in a doctor’s office or a hospital. But you only have to go once every few months:
Natalizumab (Tysabri) and ocrelizumab (Ocrevus): are options if other drugs don't work for you. Natalizumab prevents immune cells from getting to your brain and spinal cord, where they can damage nerves. Ocrelizumab attacks certain B cells and stops your immune system from attacking your body. The drugs are linked to PMI, so your doctor will do blood tests to check for it.
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Alemtuzumab (Lemtrada) and mitoxantrone (Novantrone) are chemotherapy drugs designed to treat cancer.They’re an option if you don’t respond to other mediations. They curb your immune system and prevent it from attacking nerve coverings. Novantrone has an FDA "black box" warning because it can lead to heart damage and a type of leukemia.
Treating Flares
If you’re taking other medication, mild flares will eventually go away on their own. If they aren’t bothering you, you don't need to treat them.
Steroids: If a flare gets in the way of your life, your doctor may give you high-dose steroids through a vein (intravenously) or by mouth to ease your symptoms quickly. These drugs will calm the flare, but they won't slow the course of your disease. The most common ones are:
• Methylprednisolone (Solu-Medrol)
• Prednisone (Deltisone)
• ACTH (H.P. Acthar Gel)
Plasma exchange: This can help when a flare doesn’t respond to steroids. Your doctor will remove some of your blood and separate the liquid portion (called plasma) from your blood cells. The cells are mixed with a protein solution and go back into your body.(4)
Treatment of multiple sclerosis with gamma interferon: Clinical trials of alpha and beta interferon (IFN) have been undertaken in patients with MS because of evidence that a viral infection, an immunoregulatory defect, or both, may be implicated in disease activity. In a double-blind, placebo-controlled crossover trial of natural alpha IFN given systemically, the number of acute exacerbations in patients with relapsing-remitting MS was reduced, but the study was complicated by the crossover design and a marked placebo effect. Natural beta IFN administered intrathecally to 10 patients appeared to prevent exacerbations; however, the study lacked a placebo-treated control group. Recently, a multicenter double-blind controlled trial of intrathecal beta IFN6 confirmed the favorable results of the earlier study. The first clinical trial of recombinant IFN in MS, in which 2 million units of alpha, IFN were given subcutaneously three times per week for 1 year, was recently completed. There was no therapeutic effect, possibly because the dose was too low. Other studies, using higher systemic doses of recombinant IFN, are in progress.(5)
References
1. Goldenberg MMJP, Therapeutics. Multiple sclerosis review. 2012;37(3):175.
2. Murphy R, O’Donoghue S, Counihan T, McDonald C, Calabresi PA, Ahmed MA, et al. Neuropsychiatric syndromes of multiple sclerosis. 2017;88(8):697-708.
3. Minden SL, Schiffer RBJAon. Affective disorders in multiple sclerosis review and recommendations for clinical research. 1990;47(1):98-104.
4. WebMD. Treatments for Multiple Sclerosis 2018, March 13 [Available from: https://www.webmd.com/multiple-sclerosis/ms-treatment#1 (https://www.webmd.com/multiple-sclerosis/ms-treatment).
5. Panitch HS, Hirsch RL, Schindler J, Johnson KP. Treatment of multiple sclerosis with gamma interferon. Exacerbations associated with activation of the immune system. 1987;37(7):1097-.
By Ahmed_Alzubaidy