Here I shall try to give you a broad overview of Multiple Sclerosis (MS). Multiple sclerosis is a demyelinating disease of the central nervous system (CNS). In the CNS, the axons are covered by myelin. The axon is the long slender projection of the nerve cell (neuron) that conduct’s nerve impulses away from the body of the cell. The axons in the CNS are coated / covered with myelin, an electrically insulating layer made of phopholipids (a kind of fat). Schwann cells supply the myelin for peripheral neurons ( neurons outside the brain), whereas oligodendrocytes ( a type of cell found in the brain) supply myelin for axons of the CNS.
MS is characterized by demyelination of these axons, that is some process starts to destroy the myelin leading to loss of myelin. As the disease progresses even axons get destroyed.
Just what sets off this process is still not clear. Various infectious agents and environmental factors have been postulated but none conclusively linked to MS causation. As a disease MS is more common in Caucasians and more common as you head further from the equator both in the Northern and Southern hemisphere. Thus the incidence of disease is more in Ireland than say in Sub-Saharan Africa. Why you may ask and the answer is no one knows. Maybe it is an environment factor.
Fifteen years of age is the cut off. So if you were born in a country which has a low incidence of MS such as in Asia or Africa and then emigrate to a country with a higher incidence of MS such as Ireland or Canada after the age of 15, you shall carry that low risk of the country of birth with you but if you emigrated say around 6 years then your risks of developing MS go up to the risk of a native in Ireland or Canada.
MS is more common in women as compared to men but when it does occur in men it is usually more severe.
Clinical presenting features of MS-MS has been rightly called the great mimicker in neurology. It can present with a myriad of clinical signs and symptoms which are referrable to both the brain as well as the spinal cord. MS typically presents in the following ways:
1) Isolated attack of optic neuritis: the usual history is a young to middle aged woman who presents with sudden and rapid onset of loss of vision in one eye at times associated with pain on moving the eyes. This occurs due to demyelination of the optic nerve (the nerve which is involved in vision). If the attack remains confined to the optic nerve, this is referred to as a Clinically Isolated Syndrome (CIS). Not all patients with a CIS go on to develop MS, as there are other causes of optic neuritis besides MS.
2) Numbness or weakness in one part of the body.
3) Visual complaints like double vision (diplopia), eyes not moving well (weakness of a muscle of the eye).
4) problems with balance and coordination.
5) ataxia and tremors (patients have a prominent tremor in their hands or in their trunk, as well as are off balance while standing or walking). This is due to involvement of the cerebellum and cerebellar pathways by the MS demyelinating process.
6) problems with bladder control leading to urinary incontinence.
7) Weakness in the legs (paraplegia or paraparesis)–if MS involves the spinal cord, it may cause weakness of both the legs. This condition is referred to transverse myelitis or transverse myelopathy.
So what are the presenting features of MS? MS can present in various fashions, at times the presenting features are vague and this may lead to a delay in diagnosis. The commom presenting features of MS are as follows:
1) MS may present acutely as an attack of optic neuritis. Opitic neuritis is inflammation of the optic nerve and hence the patient seeks medical attention for acute loss of vision and pain in the eye. If this occurs in a young women or man, MS should be borne in mind though there are numerous other causes of loss of vision. Patient may also complain of a desaturation of the color red ie the color red does not appear as bright and ” red” as it used to.
All attacks of optic neuritis do not necessarily lead to MS. Hence this limited presentation at onset is referred to by doctors as a ” clinically isolated syndrome“.
To be certain that your presentation is indeed isolated, your doctor shall have to take a thorough history to make sure you have never had any other attacks suggestive of MS in the past. MRI of the brain and spine as well examination of the cerebro spinal fluid is carried out to rule out any other silent lesions of MS. If no other lesions/ plaques of MS are found in the brain or spinal cord on MRI and the spinal fluid comes back normal then and only then one has a clinically isolated syndrome.
Patients who have a clinically isolated syndrome do not warrant treatment with MS specific drugs like interferons. Your doctor might give you a short course of IV and oral steroids to hasten the recovery of eye function. Most patients who have optic neuritis regain their visual acuity.
2) Numbness or weakness in an arm or leg; patients with MS may present initially with complaints of numbness or weakness in an arm or leg. This usually occurs due to involvement of motor and sensory pathways in the brain or spinal cord by MS lesions.
3) Weakness in legs: if the MS lesions involve the spinal cord, patients may present with more symmetrical involvment like numbness or weaknes in both legs (paraparesis). This condition in which MS lesions are seen in the spinal cord is referred to acute transverse myelitis.
4) Problems with balance and incoordination; MS lesions frequently involve those parts of the brain which control balance and coordination (cerebellum). Thus MS patients frequently have problems with balance and are ataxic ( drunken like gait). They have a prominent tremor in their hands and feet especially when they try to reach out to touch something. These problems with gait and balance are one of the major causes of disability and morbidity in patients with MS.
5) urinary incontinence and sexual dysfunction: MS patients may experience erectile dysfunction and urinary incontinence is very common in female MS patients.
6) Double vision: MS patients may complain of seeing double (diplopia), this occurs due to involvement of tracts in the brain which control eye movements ( an example of such a tract which is frequently involved in MS is medial longitudinal fasiculus or MLF)
Thus as you can imagine MS can present with a myriad of symptoms and the diagnoisis may not be made at the first presentation. It is usually a constellation of signs and symptoms which do not localize to any one particular area in the brain or spinal cord which makes doctors think of MS as the differential diagnosis.
Thus as I stated earlier MS is a disease which is characterized by plaques (MS lesions) which are disseminated in space ( different areas in brain and spinal cord) and time (clinical attacks occur at different times in a person’s lifetime).
Diagnosis: how is the diagnosis of MS finally confirmed? Let us discuss that now. As I stated earlier if you present with certain clinical signs and symptoms your doctor may entertain the diagnosis of multiple sclerosis.
Now once the diagnosis is entertained how do you go about confirming the diagnosis. This is usually done with the aid of an MRI of the brain and spinal cord which may show the characteristic plaques of demyelination. Your doctor may also want you to get a spinal tap (lumbar puncture). Lumbar puncture or LP is a test where in a needle is inserted into your lower back to get some of the cerebro-spinal fluid (CSF). About 10-15 ml of CSF is usually removed and sent to the laboratory for various tests. We look for some markers of MS in the CSF. If they are present, they strengthen the case for MS. At times, tests like MRI brain and spinal cord as well as lumbar puncture are unrevealing or non-diagnostic, in that case your doctor may order other tests like visual evoked potential (VEP) and somatosensory evoked potential (SSEP).
Certain diseases like for example Lyme disease, sarcoidosis can mimick MS in their presentation both clinically as well as on the MRI. Hence in appropiate circumstances more tests may be ordered to rule out these conditions.
Treatment of Multiple Sclerosis: There are now many treatments available for MS. Here I shall list a few of them without going into too much detail.
Treatment of an acute attack of MS: patients may present to the hospital with an acute attack of MS. This may involve an acute episode of optic neuritis presenting with pain and visual loss in the affected eye or they may present with increased weakness or lethargy. Acute attacks of MS respond well to corticosteroids. Usually steroids are given intravenously at high doses for about 3-5 days. Steriods help in aborting the attack and hasten recovery but they do not change the natural history of the disease (meaning that the MS disease process still continues its relentless progression).
To change the natural history of the disease, drugs that modulate the immune system are used. The most commonly used drugs are :
1) Interferons–usually interferon beta 1 b or interferon beta 1 a. Interferon beta 1 b comes by the brand name of Betaseron while interferon beta 1 a comes by two brand names: Avonex and Rebiff. When compared to each other, the interferons have some difference with respect to potency, easy and frequency of administration. You doctor shall help decide which interferon is best for you. All the interferons have some common side-effects namely injection site reactions, depression, hypothyroidism etc.
2) Glatiramer acetate also called Copolymer 1 -marketed under the brand name Copaxone.
4) Natalizumab marketed under the brand name Tysabri
8 thoughts on “Multiple Sclerosis”
Thought you’d be interested in this short omega-3 video: http://www.youtube.com/watch?v=eIgNpsbvcVM
I am a big proponent of omega-3 fatty acids. Recommend fish oils to most of my stroke patients. Thank you for your comment Susan.
Mine is more of a question then a comment. I had a ,mini stroke caused by a lesion in my right frontal lobe. The steroids shrunk it and they couldn’t get a biopsy.I was taken off of the steroids to let it regrow.So far no show.They thought at first it was CNS Lymphoma but now they feel it maybe MS.I’ve been waiting over 6 months for a diagnosis. I’ve been researching every where I can to try to figure this out. One place where I left a question they wrote back to say that it maybe both. The lesion was the size of a golf ball and they felt that was too big to be a MS lesion. Anyone who may have experienced anything like this, I would love to hear from you. My next MRI is next month & I continually pray I will finally get some answers.
hmmm you are facing a tough question there. Since you did not give me all the information I shall try to reply to the best of my capability. It is true MS lesions are usually small, that said and done MS lesions at times can be very large. This condition has been called as tumefactive MS. The reason it is called tumefactive is that the lesion is so large that it resembles a brain tumor on the MRI scan.
Both MS as well as brain tumors like CNS lymphoma may respond to steroids and at times the lesion may completely disappear. I would try to secure the diagnosis of MS in other ways: were there lesions in the spine (goes more towards been MS then), was it a single lesion on the brain or were there multiple lesions (CNS lymphoma usually presents as a solitary lesion, though at times they may be multiple lesions, this is then called multicentric CNS lymphoma. MS on the other hand usually presents with multiple lesions, though at times there may be just a solitary lesion), what did the spinal fluid show? were there any other tests done like visual evoked potentials to try to rule in or rule out MS, do you have any condition which makes you immunocompromised.
The answers to the above shall help to secure the diagnosis. Like I said both MS and tumors like lymphoma respond to steroids, so the fact the lesion regressed in size does not help us much in regards to its etiology.
Hope I was able to shed some light on this for you. Feel free to contact me directly via email.
You could’ve had a tumefactive lesion for several reasons:
(1) What they thought was a TIA — I assume that’s what you meant by “mini-stroke” — could have been the acute onset of the lesion. It doesn’t look like you had histological confirmation, so there’s no real evidence right now of whether there was axon death or gliosis.
(2) Frustratingly, CSF and evoked potentials are frequently not diagnostic of a tumefactive lesion. Tumefactive lesions are often clinically isolated, in that they do not develop into a case of multiple sclerosis. A recent series looked at 31 cases of tumefactive demyelination. 3 progressed into relapsing-remitting multiple sclerosis; the other 28 remitted until the 1-6yr followup, with no development to full-blown MS.
I seem to remember early CSF testing revealing oligoclonal banding, but followup CSF testing showing a clear immune response. In other words, unless you have more lesions or a brain biopsy, you may not ever have a “hard” diagnosis of what happened to you.
(3) You might have a specialized neuroradiologist review your MRI. If you had “horseshoe” enhancement of the lesion — essentially, a lesion whose contrast enhancement stops at the border between grey and white matter — there’s a chance that you could get a “harder” diagnosis than you have right now.
However, there’s a good chance that you’re going to have a big question mark written on your chart (or something like “idiopathic tumefactive contrast-enhancing lesion,” which is medical longhand for a question mark) until you have more neurological symptoms.
Hi, I have enjoyed reading the information you posted. I have a few questions of my own:
At this point, I have an MRI with 8 lesions, one possibly of which is tumefactive MS, a postive LP for oligoclonal bands, and my neurologist has diagnosed me with “clinically isolated syndrome”…not full blown MS at this point, but still wants to begin treatment.
1. Is tumefactive MS considered more fatal or harder to treat than “regular” MS?
2. How many oligoclonal bands are needed for a low amount? High amount? My report states greater than 3 bands. Why is there not a specific number given?
3. I have been given the choice between Rebif and Copaxone. Which is the better treatment?
thank you for writing in. You ask some very specific questions and that is what I shall attempt to answer. I am not sure why your doctor has stil labelled you as a clinically isolated syndrome (likely it is because you have had only one clinical attack suggestive of MS). Your MRI though does show dissemination of the disease in space (you can read more about the clinical diagnosis of MS on my website http://braindiseases.info) and you have more than 3 oligoclonal bands in your CSF. Now to answer your first question. Some patients have large sized demyelinating plaques (lesions) on their MRI. This is commonly referred to as tumefactive MS (because on the MRI, the lesion is large and resembles a tumor more which it has to be differentiated). There is some data to suggest that MS patients with tumefactive disease have a more aggressive disease course. Though I have to add that this data is not robust.
Oligoclonal bands are frequently present in the CSF of MS patients. Here I have to add that oligoclonal bands can be seen in many other conditions other than MS hence one has to make sure that they are present only in the CSF and not in the blood (In MS these bands are produced intrathecally meaning present only in CSF but not in blood). One study suggested that low or absent number of oligoclonal bands in the cerebrospinal fluid at the time of diagnosis predicts a better prognosis. However quantification of oligoclonal bands in the CSF remains an insensitive prognostic indicator and hence should not be used to influence decisions regarding treatment.
Now to your third question. There is some evidence to suggest that higher dose interferon (Betaseron/ Rebif) are more effective as compared to lower dose interferon. The interferons as well as Copaxone are recommened for initial treatment of relapsing remitting MS. Most of the times it is the patient’s lifestyle, easy of administration and side-effect profile which determines the choice between them.
I hope that helps you out and feel free to write again. I wish you the best.
Nitin Sethi, MD
I have been having symptoms for the past several years that appear to be MS like. I went to see a neurologist and he sent me for a MRI. During my follow-up, he told me that I had some white matter on my MRI that may be symptomatic of MS. He also sent me for some blood work. My ACE test was elevated to 80. My doctor told me that I may not have MS, but a autoimmunize illness instead. I looked up this test on the Internet and found that Sarcoidosis could be the issue. Many of the symptoms appear to be similiar to mine. My question is can sarcoidosis also cause white matter on the brain like MS?