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Only 39 Percent of Newly Diagnosed Patients Receive a Drug Within One Year of Their First Diagnosis, According to a New Report from Decision Resources WALTHAM, Mass., April 15 /PRNewswire/ -- Decision Resources, one of the world's leading research and advisory firms focusing on pharmaceutical and healthcare issues, finds that surveyed neurologists anticipate that less than 30 percent of their use of emerging oral agents --- Merck Serono's oral cladribine, Novartis/Mitsubishi Pharma's fingolimod (FTY-720) --- for the treatment of multiple sclerosis will be in the first line. Surveyed neurologists expect to use these drugs in patients who refuse injectables, filling an important unmet need and potentially increasing the drug-treatment rate in newly diagnosed patients. "Surveyed neurologists' responses suggest that Biogen Idec's Avonex is more at-risk than Teva's Copaxone of losing share upon the launch of either oral cladribine or fingolimod, as more physicians cite Avonex as having potential for being replaced by either emerging oral agent," stated Amanda Puffer, M.Sc., analyst at Decision Resources. "However, approximately half of the surveyed neurologists who are aware of these therapies are unsure if they will prescribe them, most likely because of uncertainty about these agents' side-effect/safety profiles." The new report entitled Treatment Algorithms in Multiple Sclerosis also finds that only 38.8 percent of newly diagnosed patients receive a drug within one year of their first diagnosis. This highlights the substantial room for increased uptake of disease-modifying therapies in newly diagnosed patients. While surveyed neurologists indicate they prescribe disease-modifying therapies to the majority of relapsing-remitting patients (the dominant multiple sclerosis subtype), they are less likely to prescribe disease-modifying therapies to patients with clinically isolated syndrome (early-stage multiple sclerosis). This is despite clinical studies indicating that early initiation of disease-modifying therapies can delay progression of the disease, and specifically, delay disability progression. "Those patients who do not start disease-modifying treatment right away represent an untapped opportunity for marketers of disease-modifying drugs," added Ms. Puffer. "Treatment rates could be improved, especially for patients with early stage disease, through increased awareness among both neurologists and primary care physicians, of the benefits surrounding early treatment initiation. These improvements would facilitate increased use of disease-modifying therapies." About Treatment Algorithm Insight Series Decision Resources combines in-depth primary research with the most extensive claims-based longitudinal patient-level data from IMS Lifelink: Health Plans Claims database to provide exceptional insight into physicians' prescribing trends and the factors that drive therapy product choice, from diagnosis through multiple courses of treatment, for a specific disease. About Decision Resources Decision Resources (www.DecisionResources.com) is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources, Inc. company. About Decision Resources, Inc. Decision Resources, Inc. is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources, Inc. at www.DecisionResourcesInc.com. All company, brand or product names contained in this document may be trademarks or registered trademarks of their respective holders. For more information, contact: Natalia Morales Elizabeth Marshall Decision Resources Decision Resources, Inc. 781-296-2691 781-296-2563 nmorales@dresources.com emarshall@dresources.com Website: http://www.decisionresources.com/
Some of these are very promising indeed and the current mood in MS research is very optimistic - we can look forward to more effective treatments in the near future.
However I will deal with these in a later section - in this section I will concentrate on the so-called "ABC" treatments and steroids. These are not the only treatments for MS - there are many treatments for the specific symptoms such as spasticity, vertigo, fatigue or depression and I will deal with them in the next section.
Here I want to look at treatments that affect the process of demyelination and control of relapses.
ABC Treatments Perhaps the most effective treatments currently available today deal with the autoimmune component of multiple sclerosis and work by regulating aspects of the immune system. They are known as the "ABC" treatments, where "A" stands for Avonex, "B" stands for Betaseron/Betaferon and "C" stands for Copaxone.
Avonex and Betaseron are both varieties of beta interferon. A third drug, Rebif, is also beta interferon. ABCR would be a more accurate acronym though clearly less appealing to those of us with a crossword-solving mentality.
Copaxone is a completely different drug altogether - the active ingredient being glatiramer acetate, Co-polymer-1 or COP-1.
A fifth drug, Novantrone, has recently become available. This is a chemotherapeutic agent which I shall deal with in a later section.
Beta interferon
Beta Interferon comes in two varieties, beta interferon-1a (Avonex and Rebif) and beta interferon-1b (Betaseron in the US and Betaferon in Europe).
Beta interferon (IFN-b) is a naturally occurring biochemical in the human body and belongs to a group of biochemicals known as interferons (IFNs) which regulate the functioning of the immune system.
The mechanism by which IFN-b functions is complex and not fully understood. I shall explore this more fully in a later section but for now we can summarise it as:
It reduces the levels of another interferon, called interferon gamma (IFN-g), which is known to be associated with the disease process in multiple sclerosis.
It appears to block certain white blood cells from attacking the insulating sheaths of the nerves - the myelin sheaths.
It appears to stop a type of white blood cell, called a T Cell, from releasing immune system signaling molecules (cytokines) that would otherwise encourage inflammation.
It appears to interfere with the process of summoning new immune system cells to the site of inflammation.
Read more to come:
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11. Diagnosing Multiple Sclerosis Part #6
So is getting MS just a question of where you're born?
Of course not. It's at least as much who you are as it is where you're brought up. It's your genetic make up interacting with some unknown environmental factors only one of which is where you are raised. Who you are is inevitably a product of who your parents are and who their parents are. In this section I intend to go through some of the non-geographical risk factors involved in developing MS and associated with MS relapses. As with the last section, most of this information is based on statistical data, a topic I will go into later.
So what are these risk factors?
Perhaps the most obvious risk factor is female sex. Results from data on the correlation between gender and MS varies significantly from country to country and from survey to survey. This strikes me as rather odd, since sex is a rather obvious variant and there is no shortage of PwMS to perform such a simple analysis. In all studies, MS affects women more than men, but the female to male ratio varies from 2.79:1 down to 1.65:1. It is possible that this is explainable by statistical clustering but there could be something else at play here. Many people in the UK, some neurologists and the MS Society of Great Britain included, believe that the female to male ratio in the UK is 1.5:1, but I have found no evidence to support this belief on MedLine and only a lot studies confirming the 2:1 ratio reported from other countries.
The sub-group of PwMS with the Primary Progressive form of the disease do exhibit a different gender ratio to those with other forms of the disease. Again statistics for these ratios are subject to the usual vagaries, but, in general, it seems that men are at much at risk of getting PPMS as women.
Why do women get MS more than men?
This is yet another question that is difficult to answer without knowing what causes MS in either sex. There is compelling evidence that there is, at least, some autoimmune component to the disease. Most autoimmune diseases affect women more than men and often the female to male ratio is much greater than it is in MS. The different and more variable nature of the biochemistry of women's bodies is likely to play a role especially since the naturally occurring sexual hormones oestrogen, progesterone and testosterone all have an immuno-modulating function.
It is also the case that women's genetic make-up is different to men's, having two X-chromosomes whereas men have one X- and one Y-chromosome. Whether one or more of the hypothetical multi-factorial genes that confer an increased risk of MS or other autoimmune diseases lies on the X-chromosome is something worth considering.
So if female hormones affect the risk of developing MS, does pregnancy affect MS?
Indeed it does. Several studies have examined the influence of pregnancy on multiple sclerosis and their results do not, in the main, countenance against women with MS getting pregnant. Surveys of relapse rates as well as MRI scans confirm that pregnancy, itself, significantly reduces the chances of having a relapse. Furthermore, synthetic estradiol (a commonly prescribed form of oestrogen) drug trials in women has also been shown to reduce relapse rates. This is very promising for women, but obviously rather less so for men.
So does pregnancy slow down the course of the disease?
Well, yes and no. During pregnancy relapse rates are reduced but in the three months after birth it rises significantly before falling back to the pre-pregnancy levels. So, although pregnancy and childbirth cause changes in relapse rate, they have no long term effect on the overall course of the disease. [Confavreux et al, 1998]
Reseach into other associated factors such as breastfeeding [Nelson et al, 1988] and epidural pain treatments [Confavreux et al, 1998] show them to have no effect on the course of MS. Nor does the mother having MS seem to have any negative consequences for the health of the child beyond an increased risk of developing the disease.
Of course, bringing up children is demanding and tiring work and MS itself can cause chronic fatigue as well as other disabilities which may make the nature of parenthood slightly different to that of people without MS. Couples where one or both members have MS need to consider such factors and it may well be that a partner without MS has to take on more responsibilities than would otherwise be expected. However, many PwMS successfully have families and there is no evidence that the children are in anyway damaged by having a parent with MS.
Some neurologists and other health care professionals have, in the past, advised women against getting pregnant, but various surveys show this caution to be unfounded.
But what are the risks that my children will will develop MS? People who have relatives with multiple sclerosis are more likely to develop the disease than people with no family history of MS. It seems clear from various population studies that there is a genetic susceptibilty involved in contracting the disease.
This does not mean, however, that MS is a genetic disease in the way that cystic fibrosis or sickle cell aenemia are genetic diseases. Let me try and explain why.
Humans, in common with other sexually reproducing animals, have two copies of most genes. For example, we all have two copies of the gene responsible for eye colour. Similarly, we all have two copies of a gene responsible for normal functioning of the mucus glands. However, in cystic fibrosis, a genetic disease, there has been a mutation to this gene. People who have just one copy of this abnormal gene will be perfectly healthy but people with two copies of this gene will always get cystic fibrosis.
This is a 100% certain - there are no cases of people with two copies of the cystic fibrosis mutation who do not have the disease.
Multiple Sclerosis, in common with most other autoimmune conditions, is not like this. Despite the fact that there appears an inherited risk of contracting MS, it is clear that even people with a genetic predisposition to contract MS only have a one chance in three of getting the disease. We know this from studies of identical twins in which one twin has MS. It turns out that the other twin only gets MS in 66%
Having a child is a beautiful and rewarding experience and it is my belief that
12. Diagnosing Multiple Sclerosis Part #5
Here is another inportant article about MS .Hope this helps you to get a better idea on MS .
A Biological Primer for Multiple Sclerosis
Before I get into too much detail about specific subjects, I'd like to go through some basic biology to be sure that we're all reading from the same page of the same prayer book. In this section, I want to look at genes, proteins and cells because they are important to the understanding of what multiple sclerosis is doing at the microscopic level. Hopefully, it will help you to read medical papers and take a proactive role in the management of your own disease.
Genes
Genes and microchips have been the buzz-words of the second half of the 20th century. At the end of World War II, the former had not been discovered and the latter had not been invented. The impact that these two concepts have had on our lives cannot be understated. Needless to say, I have no intention of discussing microchips here.
Let's go back almost 150 years to an Austrian monk named Gregor Mendel. Mendel is one of the least recognised of the truly great biological scientists. Everyone has heard of Darwin and Crick and Watson and can describe what their work was about. Gregor Mendel, on the other hand, was unsung in his own lifetime and, outside biological circles, remains largely so, even today. Everybody has heard of genes and yet the person who first described them is often overlooked.
What Mendel did was to experimentally observe the effects of genes in action, propose their existence (although he didn't call them genes) and to describe the broad mechanisms of their behaviour.
In 1856, he began working in a monastry flower garden and performed a number of carefully controlled breeding experiments with sweet-peas. His methods were extremely rigorous. He proposed that the existence of characteristics such as blossom colour is due to the occurrence of paired elementary units of heredity. Mendel presented his work in 1865 and it was only really noticed and validated in 1900 some years after he had died.
We now know that what Mendel found out applies to most multi-celled organisms – including all plants and animals. Though they don’t always obey Mendel’s rules of inheritance, we now know that genes, in combination with the environment, determine the appearance, constitution and behaviour of all life on earth from the tiniest virus to the great blue whale.
For most inherited traits, there are two underlying genes. These two genes can be the same as eachother or slightly different but only one version will be expressed in the animal. Mendel proposed that certain genes were dominant over others. If an organism had both a gene for a dominant characteristic and a gene for a recessive one, then only the dominant gene would be expressed to the exclusion of the recessive one. Genes that behave in this manner are known as Mendelian genes. Different possible variations for any trait are known as alelles of eachother.
Without directly observing them, Mendel had inferred the existence of genes and showed that the phenotype (the external character of an organism) is distinct from, but causally related to, its genotype (the genes that an organism carries). Subsequently, however, only the minority of characteristics have been found to follow the simple dominant-recessive pattern that Mendel described. Some genes are only partially dominant over others and both alleles (the alternative genes) can be expressed. Most characteristics are the product of several genes acting together but often, each of these operates in a Mendelian way.
DNA and genes
Nearly one hundred years later, Francis Crick and James Watson, working in Cambridge University, England, mapped out both the chemical and physical structure of DNA. This fascinating molecule contained the ingredients that explain all of Mendel's observations.
DNA has two remarkable features. It holds chemical codes for the manufacture of cellular chemicals and it is able to make near perfect copies of itself - to replicate itself. It is even more remarkable because these two functions are not performed by different parts of the DNA: they are rolled into one - the codes themselves are capable of self-replication. Both these processes are astonishingly elegant, astonishingly sophisticated and just plain astonishing. I'll try to convey the basics of them both although I won't go into much detail as cellular biochemistry is extremely complex (even the experts don't fully understand what is going on).
DNA is double stranded helix rather like a twisted rope ladder (see figures 1 above and 2 below). Each of the two parallel rope uprights is kept apart from and connected to the other by the wooden steps. All of the steps are the same width but are made of two parts joined at the middle. There are four different kinds of half step which are called “bases” because of their chemical nature. The four bases are, Adenine (A), Thymine (T), Cytosine (C) and Guanine (G). Adenine always joins to Thymine and Cytosine always joins to Guanine giving the ladder four possible types of step – called “base pairs” - AT, TA, CG and GC.
Along the beams of the ladder, the bases are organised in groups of three known as triplets or codons. Because there are four possible bases, there are 64 possible codons, all but three of which act as codes for the production of a type of chemical known as an amino acid. The three exceptions behave as 'stop' codes that terminate the production of these amino acids. In animals, there are 20 different amino acids most of which are coded for by more than one codon. A group of codons terminated by a stop code is known as a gene.
At a time appropriate to the biochemistry of the cell that contains the DNA, a gene will be transcribed from the DNA into a similar chemical called ribonucleic acid (RNA). From the RNA, amino acids are produced and are joined together to form something called a protein. Other chemicals are often combined with the protein - for example, iron in haemoglobin. You will often see proteins called peptides, polypeptides and oligopeptides. Technically, an oligopeptide has fewer than 10 amino acids, a polypeptide has between 10 and 50 amino acids and a protein has more than 50 amino acids. They are all peptides. In lay speak, oligopeptides and polypeptides are often simply called small proteins.
Almost every cell in our bodies has a nucleus which holds our genetic material strung into long tight-wound lengths called chromosomes. Every chromosome has an equivalent pair which holds the equivalent genes (alleles) that we discussed above. Human beings have 23 pairs of chromosomes - other animals and plants have a different number. Bacteria and viruses have but a single copy of each of their genes.
Proteins As we have seen, proteins are not just a dietary food-group. They are the things that make us who we are. Our skin, hair, nails, haemoglobin, blood-factors, cell walls, cell signalling messages, bones - in fact, the key constituents of our bodies are proteins. Most of your proteins are identical to mine. Most of a chimpanzee's and a fair proportion of a cabbage's proteins are also identical. However, what makes me different to you and both of us totally different to a cabbage comes from the difference in our proteins and, as a consequence, the difference in our genes.
Proteins can get very big indeed and fold up into complex bundles like tangled string. The example shown is a protein called Human Leukocyte Antigen (HLA). In fact, it is comprised of more than one component protein and is important to the functioning of the immune system. Some of the genes that code for HLA are believed to confer a susceptibility to multiple sclerosis. I shall explain more about HLA in the section on the immune system.
Last Modified: 01/21/2008 09:41:33
13. Multiple Sclerosis Prognosis Part #4
This is another part of information that I have found about MS that I would pass along os you would have a better understanding of MS. What's it going to do to me?
So what will multiple sclerosis do me?
This is a subject that is rarely brought up on the forums that I have frequented and it's also something that is hard to elucidate from Internet sources. I guess this is partly because a lot of people deal with MS by living in the present - there's no point dwelling on an unpredictable future if you can make the present into a good place to be. However the main reason that it's hard to get hold of any forecasts for the course of MS, is that it is, by its very nature, unpredictable.
Predicting multiple sclerosis is like forecasting the British weather. If you've spent much time on these islands you'll understand how fickle the weather here can be. Weathermen can only give the vaguest of indications of how things may turn out and, even then, only for the next few days. MS is similar - you can say that a number of factors are correlated with a poorer disease outcome but not with a great degree of certainty. Long-term benign disease courses can suddenly become progressive just as malignant courses can suddenly reach plateaux. With MS, nothing is certain
. Before delving into which indicators statistically lead to better or poorer outcomes, I would like to emphasise that these results are derived from statistics, and, as I shall demonstrate later, statistics should always be taken with a healthy measure of scepticism. See my section on MS and statistics. Furthermore, the inputs to these statistics are unquestionably non-parametric and multivariate and as such especially liable to error. This is born out by the results in the prognostic studies - some of which flatly contradict others and only a few indicators of disease outcome are common to all the studies.
Additionally, because of the perverse nature of this disease, you cannot say with any degree of certainty that, even if you match with some of the negative factors, that MS is going to be malignant for you. For example, there are plenty of men who have a benign disease course and yet, statistically, male sex is one of the factors correlated with relatively a fast progression. Remember also that 75% of PwMS will never need to use a wheelchair and that the majority of us will not die from MS, either directly or indirectly.
It is important to note that most of the studies, from which I draw my data from in this section, were conducted before the so-called ABC treatments (see next section) were in common usage. The effects that these drugs will have on long-term prognosis are not clearly defined, but it is safe bet that they will generally improve the disease course for people who use them. Furthermore, there is a vast amount of research work going on at the moment, which will, in all likelihood, result in treatments that will further improve the prognosis. It's an odd thing to say, but there's never been a better time to be diagnosed with multiple sclerosis.
My own personal philosophy that there is little point dwelling on potential futures because the present is where you are at just right now. Don't miss out on that. We are all mortal whether or not you have MS. Take whatever actions you can to slowdown the progression of the disease and then get on with living. As one wise PwMS said, "Hope for the best, but prepare for the worst".
Stop waffling, tell me what these indicators are!
Factors indicative of a benign disease course:
Initial symptoms purely sensory or optic neuritis.
A long interval between the first two relapses.
Disease onset before 25 years of age.
Few lesions showing on MRI scan onset
Low number of affected neurological systems 5 years after onset
Low neurological deficit score 5 years after onset High degree of remission from the last relapse
The absence of Myelin Basic Protein (MBP) in the cerebrospinal fluid (CSF) during remissions.
Onset symptoms from only one region.
Female sex.
Factors indicative of a malignant disease course:
A greater number of neurological areas affected at onset.
Many lesions showing on MRI scan at onset Pyramidal, cerebellar and sphincter involvement at onset.
Co-ordination symptoms at onset.
Progressive disease course at onset.
Oligoclonal banding in spinal tap present in the early phases of the disease.
Disease onset after 40 years of age. Less than one year interval between the first two relapses. Motor symptoms at onset. Brainstem involvement at onset.
Male sex.
The presence of sensory symptoms in addition to motor and/or co-ordination symptoms at onset indicate a better prognosis than co-ordination and/or motor symptoms alone.
Most people's disease course lies somewhere in between benign and malignant and a person's disease may have features that belong to both sets of indicators.
In general, it seems that one of the better indicators of an individual's future disease course is their past disease course. If your disease progression has been slow so far, then it will be more likely to continue to be slow than if it has been aggressive in the past.
The Expanded Disability Status Scale (EDSS) scale It may be useful to describe the Expanded Disability Status Scale (EDSS) at this point. The EDSS is a method to evaluate a person's disability numerically. The Kurtze EDSS is now accepted as the standard scale and has replaced previous scales because it gives a more even spread of disabilities. Previous scales used to bunch people up in the lower brackets.
A patient is evaluated on the EDSS according to signs and symptoms observed during a standard neurological examination. These clinical observations are classified in Functional Systems (FS). There are eight Functional Systems, each of them grading signs and symptoms for different neurological functions. The eight FS are pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other.
Kurtze Expanded Disability Status Scale
EDSS Level Description
0.0 Normal neurological examination
1.0 No disability, minimal signs in one FS
1.5 No disability, minimal signs in more than one FS
2.0 Minimal disability in one FS
2.5 Mild disability in one FS or minimal disability in two FS
3.0 Moderate disability in one FS, or mild disability in three or four FS. Fully ambulatory
3.5 Fully ambulatory but with moderate disability in one FS and more than minimal disability in several others
4.0 Fully ambulatory without aid, self-sufficient, up and about some 12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters
4.5 Fully ambulatory without aid, up and about much of the day, able to work a full day, may otherwise have some limitation of full activity or require minimal assistance; characterized by relatively severe disability; able to walk without aid or rest some 300 meters.
5.0 Ambulatory without aid or rest for about 200 meters; disability severe enough to impair full daily activities (work a full day without special provisions)
5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to preclude full daily activities
6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting
6.5 Constant bilateral assistance (canes, crutches, braces) required to walk about 20 meters without resting
7.0 Unable to walk beyond approximately five meters even with aid, essentially restricted to wheelchairs ; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day
7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; May require motorized wheelchair
8.0 Essentially restricted to bed or chair or perambulated in wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms
8.5 Essentially restricted to bed much of day; has some effective use of arms retains some self care functions
9.0 Confined to bed; can still communicate and eat.
9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow
10.0 Death
What is the typical course of MS? There really is no typical course for this disease. Everyone's disease is different and unique to them. However, despite the unpredictable nature of MS, one can identify different phases of the relapsing-remitting (RRMS) and secondary progressive (SPMS) forms of the disease.
We can see that during the early phases of the disease there are inflammatory lesions but these don't produce any symptoms. Neither the neurologist nor the person with MS is aware anything is wrong unless an MRI scan is done. This phase is known as asymptomatic MS. Some people's disease never progresses beyond this phase and it is only recognised that they ever had MS from autopsy. Some researchers estimate that as many as 40% of all people with MS have asymptomatic multiple sclerosis.
As the disease progresses to the relapsing-remitting phase, some of the inflammatory attacks start to produce symptoms - these are the relapses - although most inflammatory lesions still fall below a clinical threshold. These silent lesions outnumber symptomatic lesions in a ratio of 25:1. Again, for some people, MS never progresses beyond this phase.
As time goes by, remission from relapses becomes incomplete and the person with MS is left with some residual deficits. This phase is known as worsening relapsing-remitting MS.
Typically, worsening RRMS is followed by secondary-progressive MS. During this phase, there are still inflammatory relapses, but in between there is a gradual worsening of symptoms. The onset of SPMS is when disability really begins to take hold as when people start to slide down the EDSS scale. As a rule of thumb, most people with RRMS have an EDSS of 3.0 or less whereas most people with SPMS have an EDSS greater than this.
During the whole course of the disease, inflammatory attacks become less and less frequent. Despite this, people with SPMS continue to deteriorate and eventually move into a secondary progressive phase where there are no more relapses.
Although it isn't possible to predict whether or at what rate any indivual will move through these phases, the following graph shows the average time spent at each EDSS level across a sample population of people with MS:
The average (mean) age of onset is thirty years old for relapsing/remitting and thirty-seven years old for primary progressive. The mean relapse rate ranges from approximately 0.5 to 0.8 relapses per year and decreases with time. Most people will recover from relapses within 4 weeks.
Mean EDSS levels of Multiple Sclerosis patients after fifteen and twenty-five years.
EDSS level Time since disease onset Fifteen Years Twenty Five Years
EDSS level less than 3 33.6% 14% EDSS level from 3 to less than 6 25.2% EDSS level from 6 to less than 8 30.7% EDSS level from 8 to less than 10 5.1% EDSS level of 10 5.4% 11% Multiple Sclerosis symptoms at presentation and during course (after Poser et al 1979)
. Deficit Reported At First Presentation During Whole Disease Course Visual/Oculomotor 49% 100%
Paresis 43% 88%
Paraesthesia 41% 87%
Incoordination 23% 82%
Genito-urinary/Bowel 10% 63%
Cerebral 4% 39%
Diagnosing MS | Back | MS Symptoms Last Modified: 01/21/2008 10:10:58 FastCounter by bCentral
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14. Diagnosing Multiple Sclerosis Part #3
IMPORTANT: One thing that you really must do if you suspect that you may have multiple sclerosis, is to get your financial house in order immediately, at once and without delay. Ensure that you have adequate Health, Disability and Life Insurance prior to turning up for any examinations or tests. If any health professional tips you off that he/she suspects MS, request that no mention is made of this in any notes until you have sorted out the insurance issues. What MS treatments there are, are expensive and if you are forced out of the workplace you will need a source of income. Once a diagnosis is made it will be too late.
"Is it easy to diagnose MS?"
Diagnosing multiple sclerosis is anything but easy. There is no specific test for multiple sclerosis and, anyway, it is not even certain that it is only one disease. To an extent, getting an MS diagnosis (dx) is a process of eliminating all other possibilities. Typically, people who have finally been diagnosed with definite MS will have been through several diagnostic stages which I shall try to deal with in this section. This process is often drawn out over months or years. This can be a very unsettling and frightening period for the PwMS - the uncertainty can be very difficult to deal with. Inevitably, I draw heavily on personal experience here - the fears, insecurities and other emotions that I went through may not apply to everyone and I certainly don't intend to shoehorn everyone with MS into my own stereotype.
"So what are the stages in getting a diagnosis?"
Usually, the first thing anyone does when they notice strange neurological symptoms is to go to see their family doctor. "It's nothing to worry about" - "It's a pinched nerve" - "It's the side effect of a virus" - "It's all in your head" - "It's a temporary side effect of a migraine" - "It's Conversion Disorder". These and many other labels are used to dismiss what are very real symptoms. I've even heard of, "You're an alcoholic in denial", being used to dismiss one poor woman suffering with MS vertigo.
Provided that they aren't dismissive of the patient, I don't blame the Primary Care Physicians - MS is a very varied disease with a score of different manifestations. It is common medical practice to assume the most likely outcome rather than the more malign possibilities. Additionally, MS has a score of differential diagnoses (conditions that present with one of more of the same symptoms as MS). PCPs aren't neurologists and they can't be expected to perform neurological examinations with the same level of expertise as neurologists can, nor are they as skilled at interpreting them. This is understandable - a General Practitioner will usually have between zero and six patients with MS on their books and, even then, rely heavily on the patient's neurologist for diagnosis and treatment. I had four neurological examinations in two months - one by my General Practitioner, one by a casualty Senior House Officer and two by neurologists. The difference in skill level was immediately apparent and, although the PCPs detected the more obvious clinical symptoms, both neurologists were able to detect very many more subtle deficits.
"Is this a difficult time for the PwMS?"
Unfortunately, yes. The process of misdiagnosis causes a lot of anxiety. We know that something is wrong - often we fear a plethora of malignant outcomes, including MS, which we generally do not understand at all well at this point in time. We certainly don't need to be told that we are making it all up. I was terrified during this stage - more so than when I finally got a diagnosis and had something to understand and come to terms with.
During this phase, the PwMS may be referred to specialists in completely the wrong field or sent off for tests for completely different conditions. This just compounds the uncertainty. The majority of PwMS first present with relapsing/remitting MS and have often completely recovered from the presenting symptoms within as little as six weeks or less. I was worried about a number of possible outcomes but wanted there to be nothing the matter. Nobody wants to have multiple sclerosis. A combination of my health care professionals' denial and my own enabled me to disregard the disease for many years. Each relapse was entirely different in nature to those that had gone before. Each time I was terrified and each time I apparently recovered completely. During this period, I moved location frequently and was never seen by the same GP twice which must have prevented each from building up a case history. Often times, the PwMS will start to doubt their own perceptions and to believe that they are indeed a hypochondriac. I know I did - it didn't do too much for my state of mind but, in a way, I'm grateful for those years of false freedom from the disease.
"So when do you get to see a neurologist?"
Sooner or later we wind up with a referral to a neurologist. For most people it is sooner than it was for me. Now come a battery of tests designed to eliminate the various differential diagnoses, some of which are more urgent or more serious than MS, others are more benign or self-limiting. Diseases like Tumour or other Cord compression, Stroke, Acute Disseminated EncephaloMyelitis (ADEM), Lyme disease, Sub-Acute Sclerosing Panencephalitis, Neurosyphilis, Progressive Multifocal Leukoencephalopathy, Systemic Lupus Erythematosus, Cerebral Arteritis, Complicated Migraine, Diabetes, Hypothyroidism, Myasthenia Gravis, Acute Transverse Myelitis, Herpes Simplex Encephalitis, Polyarteritis nodosa, Sjogren syndrome, Behcet's syndrome, Sarcoidosis, Paraneoplastic syndromes, neuromyelitis optica (Devic's syndrome), HIV-associated myelopathy, Adrenomyeloneuropathy, other Myelopathy, Spinocerebellar syndromes, Hereditary Spastic Paraparesis, Guillian Barre Syndrome, Polymyositis, Benign Paroxysmal Positional Vertigo, Parkinson's Disease, Cerebral Haemorrhage, Amyotrophic Lateral Sclerosis (ALS), Mononeuritis, Huntington's Disease, Post-Infectious Encephalitis, Arteriovenous Malformations, Arachnoid Cysts, Arnold-Chiari Malformations, Cervical Spondylosis and many more.
The first thing a neurologist will do is go through the patient's medical history and that of their family. It may well be that the patient has had previous symptoms consistent with multiple sclerosis or have relatives with the disease. This makes MS more likely. They will then ask the patient to describe their current symptoms. The patient's description of his/her symptoms is an important indicator.
The neurologist will then go through a thorough neurological examination, testing reflexes with hammers, sticking you with pins, tickling the bottom of your feet, examining you with opthalmoscopes and testing your senses with tuning forks. You are made to stand still with your eyes closed, walk heel-to-toe and your muscle strength is tested. The neurologist will be looking for specific deficits and testing for certain signs.
"What are these deficits and signs?"
There are many different neurological tests and the ones your neurologist chooses to perform will depend, in part, on the symptoms that you present with. Here are some of the more common ones.
Romberg's sign: This is a test for ataxia (incoordination or clumsiness of movement that is not the result of muscular weakness) and involves standing with your feet together with your eyes closed. Ataxics have great problems standing still under these conditions.
Gait and coordination: The neurologist evaluates ataxia in various parts of the body by observing the patient walking normally, walking heel-to-toe and finger-to-nose tests. The neurologist will also be looking for intention tremor (shaking when performing small motor movements) as well as ataxia in this last test.
Heel/Shin test: This is a test for ataxia and cerebellar dysfunction. You have to bring the ball of your heel onto the knee of your other leg and then move it down the shin.
L'Hermittes sign: This is a test for lesions on the spinal cord in the neck. The neurologist will ask you to lower your head towards your chest. A positive L'Hermittes will generate buzzing, tingling or electrical shock sensations in one or more parts of the body.
Optic Neuritis: This is a condition of the eye caused by inflammation and demyelination of the Optic Nerve and is perhaps the most commonly presenting symptom in MS. The tests involve the ubiquitous reading of letters from a board and a test for colour vision using an "Ishihara" colour chart. An examination with an opthalmoscope will reveal pallor of the optic nerve in old optic neurites.
Hearing Loss: This is done by lightly clicking the fingers next to each ear and asking the patient which ear the click was done next to.
Muscle Strength: This involves resisting the neurologist with various muscle groups. Differences in strength between left and right sides are easier to evaluate than symmetrical loss unless the weakness is severe.
Reflexes: This is done with both ends of the hammer. The reflexes can be normal, brisk, i.e. too easily evoked, or non-existent.
Babinski's sign: A test for signs of disease process in the motor neurons of the pyramidal tract. The test involves drawing a semi-sharp object along the bottom of the foot. The normal response in adults and children is for the toes to reflex downwards (flexor response). In babies and people with neurological problems of the corticospinal tract, the big toe moves upwards (extensor response).
Chaddock's Sign: Similar to Babinsky's but testing for lesions in the corticospinal tract. The neurologist touches the skin at the outside of the ankle. A positive response in upwards fanning of the big toe just like in Babinski's test.
Hoffman's sign: This is also similar to Babinski's but involves the hands rather than the feet. Again it tests for problems in the corticospinal tract. The test involves tapping the nail on the third or forth finger. A positive response is seen in flexion of terminal phalanx of thumb.
Doll's Eye Sign: The neurologist is looking for dissociation between movement of the eyes and of the head. A positive response is when the eyes moves up and head moves down.
Sensory: This is done with tuning forks and pins and tests the level of sensory perception in certain parts of your body.
"Can you get a definite diagnosis from the neurological examination?"
It is very rare to get a definite diagnosis at this stage. Certain signs and symptoms are more indicative of multiple sclerosis than others, but, assuming that you do have the disease, the most definitive dx you will get will be "probable MS". You are much more likely to get a dx of "possible MS".
The neurologist will probably book you in for several tests including MRI scans, spinal taps and evoked potential tests.
It is important to note that whatever the results of these tests or the neurological exam, it is not possible to diagnose definite MS from a single episode. There are a number of demyelinating conditions of unknown aetiology which are self-limiting and strike only once. In order to diagnose MS, there must be at least two episodes separated by at least one month and the location of the lesions must be in a least two distinct sites in the central nervous system. This means that the PwMS will, by definition, have to wait at least the period of time that separate the first two relapses that cause clinical symptoms. This could be as little as one month but is more likely to be several months or even years. Often people want a definite diagnosis, but they certainly don't want to have to have another relapse to prove it. Catch-22.
Neurologists used to use a checklist called the Schumacher criteria to confirm a diagnosis of multiple sclerosis. Though these criteria are now largely outdated, an MS diagnosis remains a clinical one and they still form the basis for later revisions. They are also worth looking at because they are the simplest statement of what MS is, clinically. The Schumacher criteria are:
Neurological examination reveals objective abnormalities of CNS function.
History indicates involvement of two or more parts of CNS.
CNS disease predominately reflects white matter involvement.
Involvement of CNS follows one of two patterns:
Two or more episodes, each lasting at least 24 hours and at least one month apart.
Slow or stepwise progression of signs and symptoms over at least 6 months.
Patient aged 10 to 50 years old at onset.
Signs and symptoms cannot be better explained by other disease process.
From Schumacher et al, 1965
The Poser criteria have updated the Schumacher criteria in recognition of the diagnostic benefits of laboratory data. They have not changed the fact that MS is still essentially a clinical diagnosis and are themselves about to be replaced by new criteria that acknowledge the importance of Magnetic Resonance Imaging (MRI). The Poser criteria are:
Clinically definite MS
2 attacks and clinical evidence of 2 separate lesions
2 attacks, clinical evidence of one and paraclinical evidence of another separate lesion
Laboratory supported Definite MS
2 attacks, either clinical or paraclinical evidence of 1 lesion, and cerebrospinal fluid (CSF) immunological abnormalities
1 attack, clinical evidence of 2 separate lesions & CSF abnormalities
1 attack, clinical evidence of 1 and paraclinical evidence of another separate lesion, and CSF abnormalities
Clinically probable MS
2 attacks and clinical evidence of 1 lesion
1 attack and clinical evidence of 2 separate lesions
1 attack, clinical evidence of 1 lesion, and paraclinical evidence of another separate lesion
Laboratory supported probable MS
2 attacks and CSF abnormalities
From Poser, 1983
Still more recently, 4th May 2001, an international panel in collaboration with the NMSS of America has recommended revising the diagnostic criteria for multiple sclerosis.
The new proposed diagnostic criteria are:
Clinical Presentation Additional Data Needed
2 or more attacks
2 or more objective clinical lesions None; clinical evidence will suffice
(additional evidence desirable but must be consistent with MS)
2 or more attacks
1 objective clinical lesion Dissemination in space, demonstrated by
MRI
or a positive CSF and 2 or more MRI lesions consistent with MS
or further clinical attack involving different site
1 attack
2 or more objective clinical lesions Dissemination in time, demonstrated by
MRI
or second clinical attack
1 attack
1 objective clinical lesion
(monosymptomatic presentation) Dissemination in space by demonstrated by
MRI
or positive CSF and 2 or more MRI lesions consistent with MS
and
Dissemination in time demonstrated by
MRI
or second clinical attack
Insidious neurological progression
suggestive of MS
(primary progressive MS 2 ) Positive CSF
and
Dissemination in space demonstrated by
MRI evidence of 9 or more T2 brain lesions
or 2 or more spinal cord lesions
or 4-8 brain and 1 spinal cord lesion
or positive VEP with 4-8 MRI lesions
or positive VEP with <4 brain lesions plus 1 spinal cord lesion
and
Dissemination in time demonstrated by
MRI
or continued progression for 1 year
"So, tell me more about the other tests."
Magnetic Resonance Imaging (MRI)
Along with the neurological exam, this is by far and away the most useful and definitive of diagnostic tools. MRI is a branch of Nuclear Magnetic Resonance (NMR) a procedure that involves detecting how molecules spin in powerful magnetic fields. MRI was first used in medicine in 1977 and, though expensive, it is unparalleled at detecting changes and abnormalities inside soft bodily tissue. Water molecules, which are present in all soft tissue, carry a small electromagnetic polarity and, as a result, act like minuscule magnets. MRI scanners exert enormously powerful magnetic fields around the patient who lies in a tube in the middle of the scanner. This causes all the water molecules to wobble and this is detected and imaged on a computer, from which it can be printed onto a negative.
MRI is completely harmless provided that you do not have any magnetic metals around your person during the scan. For more details on MRI and safety procedures, follow this link: Magnetic Resonance Imaging.
MRI scans give detailed high resolution images of cross sections of the brain and to a lesser extent, the spinal cord. Multiple Sclerosis lesions show up as paler areas on those images. From an MRI, the neurologist can not only identify that there have been probable demyelination events but can also see where those lesions are and use them to explain both present and potential signs and symptoms.
Surprisingly perhaps, and despite its accuracy, an MRI scan alone cannot be used to make a definite diagnosis of MS. Clinical symptoms are usually necessary and, because there are a number of other demyelinating conditions, these must be ruled out. As already mentioned, the clinician will also want evidence that there has been at least two identified demyelinating episodes separated by at least one month in at least two different locations in the CNS.
Nor do MRI scans always pick up MS lesions. There is evidence that some older lesions remyelinate sufficiently to be undetectable with MRI scans. Having said this, the vast majority of people with a definite dx of MS will show evidence of disease activity on MRI scans.
Spinal Tap
A spinal tap (also known as a lumbar puncture) is a procedure whereby a sample of cerebrospinal fluid (CSF) is taken from close to the spinal cord. At the same time a blood sample is taken usually from the arm and a quantity of blood serum is isolated. Both of these samples are then processed using a technique called electrophoresis. A positive spinal tap will produce oligoclonal bands in the CSF but not in the blood serum. These bands indicate a type of immune system activity. Although uncomfortable, the spinal tap itself is often not too painful, whereas in the period following the tap, the patient may experience dizziness, nausea, vomiting and severe headaches, occasionally for as much as a week. There are a few rare but serious side-effects of spinal taps. For more information about spinal taps and how to reduce the possibility of some of the more unpleasant side-effects follow this link: Spinal Tap.
95% of people with a definite diagnosis of MS exhibit oligoclonal bands on a spinal tap. This may sound impressive but so do 90% of people with Sub-Acute Sclerosing Panencephalitis and 100% of people with Herpes Simplex Encephalitis among other conditions. Positive spinal taps are indicative of an immunological response but they are not diagnostic for a particular condition. That 5% of PwMS do not exhibit oligoclonal banding means that spinal taps neither rule-in nor rule-out MS.
The primary purpose of CSF analysis should be to rule out other conditions than multiple sclerosis. Although they can be highly suggestive of MS, they do not, in themselves, provide definitive disgnosis. Indeed, I myself, was given a definite diagnosis based on medical history, clinical examination, MRI and evoked potential tests - I declined to have a spinal tap.
Before MRI, electrophoresis of spinal fluid played a major role in supporting diagnoses and underpinned the Poser criteria. Now, however, these criteria have become overshadowed by MRI and, if an MRI is positive, the new diagnostic criteria (2001) allow for a definitive diagnosis without laboratory support. The old "Laboratory supported Definite MS" has been dispensed with.
However, CSF analysis technology is still advancing and researchers continue to look for definitive molecular markers of MS. Should they find such a marker, spinal taps will reassume their importance. Other researchers are looking into urine and blood for markers and we can hope that they are successful and spinal taps become completely unnecessary to the diagnosis of multiple sclerosis.
Evoked Potential (EP) tests
Evoked Potential tests are procedures for measuring the speed of impulses along neurons. Responses can be measured using EEG readings from electrodes attached to the scalp and occasionally other areas of the skin. Although this may sound like something from Frankenstein, they are in fact completely painless and entirely harmless. Based on input signals to the particular sense being measured, the time taken for that response to register can be accurately measured and compared to normal readings. The results are then analysed on a computer and average speeds recorded.
Demyelinated neurons transmit nerve signals slower than non-demyelinated ones and this can be detected with EP tests. Although they may appear to function perfectly, even remyelinated neurons are slower than normal nerves and so historical lesions can be detected in this way.
There are three main types of evoked potential test:
Visually Evoked Potential (VEP)
This test measures the speed of the optic nerve. The patient has to focus on the centre of a "TV" screen on which there is a black and white chequered pattern. Each square in the pattern alternates between black and white at measured intervals. The patient wears a patch on one eye for a while and then on the other, so that the speed of both optic nerves can be measured.
85-90% of people with definite MS and 58% of people with probable MS will have abnormal VEP test results.
Follow this link for more information on Visually Evoked Potential.
Brainstem Auditory Evoked Response (BAER)
The BAER test measures the speed of impulses along the auditory portion of Cranial Nerve VIII. This nerve arises in the Pons area of the Brainstem and therefore this test may be indicative of lesions in that area. The patient lies down in a darkened room to prevent visual signals from interfering with measurements. A series of clicks and beeps are played back to the patient.
67% of people with definite MS and 41% of people with probable MS will have abnormal BAER test results.
Follow this link for more information on Brainstem Auditory Evoked Response.
SomatoSensory Evoked Potential (SSEP)
The SSEP test involves strapping an electrical stimulus around an arm or leg. The current is switched on for 5 seconds and electrodes on the back and skull measure the response at particular junctions. The current is very low indeed and completely painless. The speed of various nerves can be measured in this way and the points of slow-down (i.e. demyelinated lesions) approximated to because of the sampling at several places.
77% of people with definite MS and 67% of people with probable MS will have abnormal SSEP test results.
Follow this link for more information on SomatoSensory Evoked Potential.
Slow nerve responses in any of these tests are not necessarily indicative of MS but can be used in conjunction with a neurological examination, medical history, an MRI and a spinal tap to deduce some kind of diagnosis.
CT scans
Computed Tomography scans use X-rays to produce images of the brain. CT scanners look a lot like MRI scanners and are also used to produce cross-sectional images of internal parts of the body. However, CT scans detect soft body tissue with far less precision that MRI scans and their use has largely been replaced by them. Since CT scans use X-rays which are potentially very harmful, this is no bad thing. Sadly, MRI scanners are much more expensive than CT scanners and many areas where MS is relatively common do not have access to them.
Follow this link for more information on CT scans.
How does MS do its damage? | Back | Prognosis: What's it going to do to me?
Last Modified: 01/21/2008 09:48:03
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15. How does Multiple Sclerosis do its damage?
In order to understand what is happening in multiple sclerosis it is necessary to understand a little about the brain and spinal cord - collectively called the central nervous system or CNS for short.
"Ok then, tell me about the CNS"
The CNS is full of nerve cells called neurons. These are the brain cells of popular usage. Here is a simplified diagram of a neuron:
There are different types of neuron in different areas of the CNS. Those in the white matter tissue are are the ones most liable to be attacked in multiple sclerosis. This type of neuron is a long thin cell which has a bulbous head (the soma) containing the cell nucleus and an elongated strand called an axon. The soma has thin, branched tendrils called dendrites growing out of it.
The axon of one neuron joins to the dendrites of other neurons via a special connection called a synapse. Signals or nerve impulses travel down the axon where they are transmitted to other neurons via chemical signals (neurotransmitters) moving across the synapse. The axon itself, is coated with a sheath of insulating fatty protein called myelin which aids the transmission of nerve impulses. A good analogy of the myelin's relation to the axon is the plastic or rubber insulation around electric wires.
Oligodendrocytes are the axon's maintenance cells. Their job is to create and repair the myelin sheath and to feed essential factors to the axon. Each oligodendrocye maintains several axons and each axon is maintained by several oligodendrocyes.
Oligodendrocyes belong to a larger grouping of maintenance cells called glial cells. Their importance has recently become better understood and, as more and more is discovered about MS, the more central oligodendrocytes, or more accurately their death, has become. In some ways, it is fair to say that multiple sclerosis is a disease of oligodendrocytes.
"So what does MS do to the CNS?"
During periods of multiple sclerosis activity, white blood cells (leukocytes) are drawn to regions of the white matter. These initiate and take part in what is known as the inflammatory response. The resulting inflammation is similar to what happens in your skin when you get a pimple.
During the inflammation, the myelin gets stripped from the axons in a process known as demyelination. The effect of this bears many parallels to the rubber insulation on wire perishing - some or all of the electricity in the wire will short out and the efficient conductivity of the wire will be reduced. When the myelin sheath is damaged, the transmission of nerve impulses is slowed, stopped or can jump across into other demyelinated axons.
Additionally, the inflammation can also damage the underlying axonal membrane. This membrane is a sophisticated structure that enables the nerve transmission (the action potential) to travel along the nerve.
It seems that the inflammation also kills the mainenance glial cells, in particular it seems to kill the myelin-producing oligodendrocytes, which are lost in great numbers. Almost no oligodendrocytes persist in the middle of chronic MS lesions.
At least, this has been the prevailing theory for the past few years. Now, however, several pieces of experimental work have produced results which challenge this model. Inflammation and oligodendrocyte loss are both found together in multiple sclerosis but which comes first? Does inflammation cause oligodendrocyte death, does oligodendrocyte death cause inflammation or are they both caused by a third process, perhaps a virus?
Recent research has looked at the brains of people who have died in the very early stages of MS lesion development and found that oligodendrocyte death actually precedes inflammation [Prineas et al, 2004]. It must be emphasised that these are the results of a very small study which have not yet been reproduced. Although few would deny that the inflammation contributes to MS damage, this work has the potential to turn the world of MS research upside-down. It suggests that looking for an autoimmune cause for MS may be misguided. It also challenges the current anti-inflammatory focus of most MS therapies. Are we, by analogy, treating a broken pipe by sticking a bucket under it rather than fixing the leak? That's not to say that these therapies don't produce results, just that tackling inflammation may not be the optimal stategy. For people with MS, this is a space to watch eagery.
As the disease progresses, axons are also destroyed though not necessarily by the inflammatory response. During the secondary progressive phase of the disease, inflammation becomes less and less common but still the axons continue to die. This degeneration of axons is known as Wallerian Degeneration.
One theory is that the axons are dying because there are no oligodendrocytes to feed them the essential factors that they need. Perhaps the most important of these is called, Insulin-like Growth Factor-1 (IGF-1) - so-called because it resembles the sugar-regulating hormone, insulin. Experiments on rats indicate that axons deprived of IGF-1 will eventually die [Gutierrez-Ospina et al, 2002 and Russell et al, 1999].
Another factor, Brain Derived Neutrophic Factor (BDNF), has also been implicated in Wallerian degeneration. The absence of sufficient BDNF has also been linked to a variety of other degenerative diseases of the central nervous system, including Parkinson's disease and motor neuron disease. Interestingly, BDNF is naturally released by the body during vigorous exercise [Gold et al, 2003].
Recent work using newer MRI techniques has shown Wallerian Degeneration in the white matter that looks normal using the older technologies [Ciccarelli et al]. Quite what this discovery means is not yet clear but it may be a further example of the disease process enduring without inflammation.
All these processes, inflamation, demyelination, oligodendrocyte death, membrane damage and axonal death contribute to the symptoms of MS.
"Do nerves get better after demyelination?"
After axons have been demyelinated, several things can happen.
The inflammation dies back. Neurons which have not been damaged by the relapse can resume their proper function and some recovery (remission) is usual, at least in the early stages of the relapsing-remitting form of the disease.
Demyelinated axons can exhibit remarkable abilities to function despite losing their myelin. Recent work has shown that they produce greater numbers of sodium channels. These are special chemical gates which are integral in sending nerve transmissions (the action potentials) down the neuron [Moll C et al, 1991]. This increased number of sodium channels contributes to remission in MS.
The central nervous system is a very plastic organ and new neuronal pathways and connections can be created to get around the damaged neurons. This is analagous to a motorist taking a minor road to avoid a traffic accident on their intended route. Although it is clear that this mechanism contributes to remission, it is far from clear what the exact details are and much work remains to be done in this area.
The myelin maintenance cells in the CNS, the oligodendrocytes, can sponsor remyelination - a process whereby the myelin sheath around the axon is repaired. Despite the fact that evoked potential tests show that remyelinated axons don't function quite as well as those which were never damaged in the first place, to the PwMS, this is sometimes not noticeable. Although remyelination usually only occurs at the edges of lesions, it still seems to be a contributary factor in remission.
Remyelination may not take place or only happen partially, at least for a long time, due to oligodendrocytes not being around to promote it. When this happens the nerve will continue to function in an abnormal way as described above, but the axon remains undamaged. Sometimes after a long period of time, sometimes years, an axon will spontaneously become remyelinated and regain much of the function that had been presumed to be lost for good.
The lost myelin can be replaced with scar tissue much like when you cut your hand a scar forms to join the separated areas of skin. This scarification is how Multiple Sclerosis got its name: Multiple - many and Sclerosis - scar forming. Scar tissue can block the formation of new myelin and once axons have become scarified they do not fully regain their former function.
The underlying axon can become withered and function lost entirely. Needless to say a withered axon will never function at all again. Continuing our electrical wire analogy, this is rather like snipping the cable with wire cutters.
"So what causes Multiple Sclerosis?"
This is the 64 thousand dollar question of MS. There are several theories as to the cause of MS but the overall process is so poorly understood that none has yet delivered the coup-de-grace. Each new discovery seems to beg more questions than it answers. The research process advances so fast that each new iteration of this section is out of date even as I post it onto my web server.
The cause of MS is a complex subject and, later on, I will devote several sections to what I believe are valid theories. For the time being, I will simply list some of the contenders.
Autoimmunity
That MS is an autoimmune disease is the leading theory in the scientifico-medical world. "Auto" is derived from the Greek for self and autoimmunity means immune to self. When applied to MS, it means that the body's natural defences are actually attacking its own myelin. One particular theory, called molecular or epitopic mimicy, attempts to explain how the immune system might do this. Another possible explanation is that the myelin is lost in collateral damage as the immune system attacks something else.
Either way, the immune system is an incredibly complicated "organ" with many strands to its bow and is very poorly understood. Much of what is known derives from recent work done in the last 10 years or so. A friend of mine who is an immunologist working in the field said, "We are all very proud of ourselves because we have mapped out a metaphorical area the size of my back garden but that has only made us realise that the whole metaphorical immune system is the size of London".
There are a lot of very convincing reasons to believe that the immune system plays a role in the destruction of myelin.
Pathogen mediated
This is the other leading scientific theory of the mechanism for how multiple sclerosis operates. "Pathogen" is a generic word for the nasty little bacteria, virii, fungi and other microbes that cause so many other diseases. Some tantalising work has found statistically significant links to a number of virii and bacteria including Epstein-Barr virus, Human Herpes Virus 6, Clamydia Pneumonia and other pathogens.
However, there have been many false dawns in multiple sclerosis research and we must wait and see whether these (or any other pathogens) are primary instigators of the disease process or whether they are merely opportunist invaders of an already damaged CNS.
Genetic components
There is overwhelming evidence that there is a genetic component in MS and family studies show that first degree relatives of PwMS have twenty to forty times the probability of developing the disease than the observed incidence for the locality in which they grow up. However the link is rather weak compared to other inherited diseases and it is very likely that several genes are operating in tandem.
It is probable that there are more than just genes at work. Several studies have shown that, when one identical twin has MS, the other twin has only a 30% chance of developing the disease. This means that even if you inherit a susceptibility to contract MS, there is less than a third chance that you will contract the actual disease.
Despite extensive work in mapping the human genome, researchers have so far been unable to pinpoint any specific genes. However, target sections of the MS genome have been strongly implicated and we can look forward to breakthroughs in this area very soon.
In many ways, genetics, virology, bacteriology and immunology are intimately bound up with each other and it may be that a combination of all these disciplines will provide the eventual answer.
Damage to the Blood-Brain-Barrier
The Blood-Brain-Barrier (BBB) is a protective barrier formed by the cells lining the blood vessels (the endothelial cells). It allows for the exchange of oxygen, essential nutrients, carbon dioxide and other waste materials between the blood and the CNS while preventing the majority of pathogens from crossing into the brain. Researchers have shown that, under the right circumstances, everybody's immune systems will attack myelin so why doesn't everyone have MS?
Immune system cells are entering the CNS of people with MS but they are not going into the brains of others. How and why do they get there? Does this imply that the BBB has somehow become damaged or is this a normal response to something going wrong elsewhere in the body? If the damaged BBB theory is true, how does it get damaged? Is it possible that a pathogen is damaging or has damaged the BBB? Some point at trauma as a potential candidate - that the PwMS has had a fall or other mechanical injury that has damaged the BBB prior to contracting the disease.
Preventing these immune system cells from entering the central nervous system is the aim of an experimental therapy for MS, called Natalizumab (brand name Antegren).
Biochemical events in utero
It has been proposed that interactions with the foetal genome in the womb during very early life or at a later stage still prior to birth affect the development of the immune system. Recent evidence shows that some of the mother's genome can pass through into the foetus and become part of the individual. This work is very preliminary but tantalising nevertheless.
Diet and vitamin deficiencies
A number of people believe that MS is a side effect of an inappropriate diet. Various diets including the Swank diet, the Paleolithic diet, Bachmann B12 supplements, the Cari Loder treatment and the Atkins diet amongst others have been proposed as potential treatments for MS and some people claim considerable success. Most of these success stories are anecdotal and some well conducted affirmative studies are needed in this area.
Allergic reaction and other alternatives
There is no shortage of candidates for a cause of MS. Some say it is an allergic reaction and advocate histamines as a treatment - this is the idea behind Procarin. The problem is that MS is, by its very nature, unpredictable and large studies are needed to determine the veracity of many of these claims. Such studies are expensive and funding is an acutely limited resource. Some people suggest that MS is not a single disease or that, if it is a single disease, that it has multiple causes. Some of the alternative theories are very bizarre ranging from exposure to cattle and geomagnetic fields to the angle at which we sleep.
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16. Treatment for MS Part 1
Julie Stachowiak, Ph.D.
As an epidemiologist who is also a person living with MS, Julie Stachowiak, PhD has an in-depth understanding about current research and scientific developments around MS. She also has first-hand knowledge of the frustrations and anxiety surrounding the disease, as she had MS for at least 15 years before receiving a diagnosis in 2003 and has had several relapses since her diagnosis.
Experience:
Dr. Stachowiak has a long history of working on the grassroots public health level, having founded an international non-profit organization and serving on the Boards of Directors of several others. She held a faculty position at the Johns Hopkins Bloomberg School of Public Health in the Department of Epidemiology. Since being diagnosed with MS, Dr. Stachowiak has spent time learning about the disease and investigating different approaches to treatment and symptom management. She currently works as a freelance writer and consultant.
Education:
Dr. Stachowiak holds a PhD in Public Health from Johns Hopkins University. She also has a Master of Public Health (Maternal and Child Health) and a Master of International Affairs (Human Rights) from Columbia University. Her undergraduate degree is a Bachelor of Fine Arts in Graphic Design, which has given her skills in communicating abstract or difficult ideas so that they can be understood by a wide range of people.
From Julie Stachowiak, Ph.D.:
Even before my diagnosis and since finding out that I had MS, I have spent many anxiety-filled hours looking for information about the symptoms I was experiencing, what might be causing them and what was going to happen to me. I usually ended up more confused and scared than when I started looking. It is my goal to help people find answers to their questions and to understand that there is much more to life than MS. If you have MS, I want you to have whole days where you are so comfortable with your level of knowledge about MS that you do not even think once about your disease.
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Business Round-Up on Multiple Sclerosis
Wednesday February 11, 2009
I'm trying to keep up on all the business news around multiple sclerosis. I find it fascinating to see the intersection of pharmaceutical research and business. Here is the latest news on the business side of multiple sclerosis:
Biogen Idec, the makers of Tysabri and Avonex, reported an increase in profit by 3% in the fourth quarter of 2008. Given the state of things, any report of an increase in profit right now seems fabulous (and slightly magical). They earned $206.7 million (70 cents a share), which is up from the same time last year. Tysabri sales increased 73% to $156 million and Avonex sales grew 13% to $556 million.
Meanwhile, Biogen Idec's stock took a beating on news of a forthcoming oral treatment for multiple sclerosis that is reported to be more effective and safer than Tysabri
ms.about.com/od/multiplesclerosis101/a/ms_intro.htm - 30k
www.webmd.com/multiple-sclerosis/guide/recognizing-multiple-sclerosis - 149k
Multiple Sclerosis: Recognizing Multiple Sclerosis
Multiple sclerosis symptoms generally appear between the ages of 20 and 40. The onset of MS may be dramatic or so mild that a person doesn't even notice any symptoms until far later in the course of the disease.
The most common early symptoms of MS include:
Tingling
Numbness
Loss of balance
Weakness in one or more limbs
Blurred or double vision
Less common symptoms of MS may include
Slurred speech
Sudden onset of paralysis
Lack of coordination
Cognitive difficulties
As the disease progresses, other symptoms may include muscle spasms, sensitivity to heat, fatigue, changes in thinking or perception, and sexual disturbances.
Fatigue . This is the most common symptom of MS. It is typically present in the mid afternoon and may consist of increased muscle weakness, mental fatigue, sleepiness, or drowsiness.
Heat sensitivity . Heat sensitivity (the appearance or worsening of symptoms when exposed to heat, like a hot shower) occurs in most people with MS.
Spasticity . Muscle spasms are a common and often debilitating symptom of MS. Spasticity usually affects the muscles of the legs and arms, and may interfere with a persons ability to move those muscles freely.
Dizziness. Many people with MS complain of feeling "off balance" or lightheaded. Occasionally they may experience the feeling that they or their surroundings are spinning; this is called vertigo. These symptoms are caused by damage in the complex nerve pathways that coordinate vision and other inputs into the brain that are needed to maintain balance.
Impaired thinking . Problems with thinking occur in about half of people with MS. For most, this means slowed thinking, decreased concentration, or decreased memory. Approximately 10% of people with the disease have severe impairment that significantly impairs their ability to carry out tasks of daily living.
Vision problems . Vision problems are relatively common in people with MS. In fact, one vision problem, optic neuritis, occurs in 55% of people with the condition. Most vision problems do not lead to blindness.
Abnormal sensations. Many people with MS experience abnormal sensations such as "pins and needles," numbness, itching, burning, stabbing, or tearing pains. Fortunately, most of these symptoms, while aggravating, are not life-threatening or debilitating and can be managed or treated.
Speech and swallowing problems . People with MS often have swallowing difficulties. In many cases, they are associated with speech problems as well. They are caused by damaged nerves that normally aid in performing these tasks.
Tremors . Fairly common in people with MS, tremors can be debilitating and difficult to treat.
Difficulty walking. Gait disturbances are amongst the most common symptoms of MS. Mostly this problem is related to muscle weakness and/or spasticity, but having balance problems or numbness in your feet can also make walking difficult.
Other rare symptoms include breathing problems and seizures
Multiple Sclerosis: Recognizing Multiple Sclerosis
(continued)
What Are the Types of Symptoms?
It is helpful to divide the symptoms into three categories: primary, secondary, and tertiary.
Primary symptoms are a direct result of the demyelination process. This impairs the transmission of electrical signals to muscles (to allow them to move appropriately) and the organs of the body (allowing them to perform normal functions.) The symptoms include: weakness, tremors, tingling, numbness, loss of balance, vision impairment, paralysis, and bladder or bowel problems. Medication, rehabilitation, and other treatments can help keep many of these symptoms under control.
Secondary symptoms result from primary symptoms. For example, paralysis (a primary symptom) can lead to bedsores (pressure sores) and bladder or urinary incontinence problems can cause frequent, recurring urinary tract infections. These symptoms can be treated, but the ideal goal is to avoid them by treating the primary symptoms.
Tertiary symptoms are the social, psychological, and vocational complications associated with the primary and secondary symptoms. Depression, for example, is a common problem among people with MS.
What Causes the Symptoms?
Demyelination, or deterioration of the protective sheath that surrounds nerve fibers, can occur in any part of the brain or spinal cord. The symptoms that people with MS experience depend on the affected area. Demyelination in the nerves that send messages to the muscles causes problems with movement (motor symptoms), while demyelination along the nerves that carry sensory messages to the brain causes disturbances in sensation.
Are Symptoms the Same in Every Person?
Multiple sclerosis follows a varied and unpredictable course. In many people, the disease starts with a single symptom, followed by months or even years without any progression of symptoms. In others, the symptoms become worse within weeks or months.
It is important to understand that although a wide range of symptoms can occur, a given individual may experience only some of the symptoms and never have others. Some symptoms may occur once, resolve, and never return. Because MS is such an individual disease, it is not helpful to compare yourself with other people who have MS.
Reviewed by the doctors at the Mellen Center for Multiple Sclerosis Research at The Cleveland Clinic
17. HAPPY HOLIDAYS
HAPPY HOLIDAYS
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18. New Jims Corner Shop.com James Eckburg
Hi, Welcome to Jims Corner Shop.com website. I would like to introduce myself to you. I have been disabled for over 30+ years. I have been in a wheelchair since 1989. I have MS and can not walk at all. So I don’t get very much exercise because I’m in the wheelchair from the time I get up until I go to bed. I got to be close to 300 lbs and I had very severe tremors that I could not hold a pencil to write or even print my name. I came across an ad in the paper to earn some extra income over the computer so I answered it. I received a weight management program from Herbalife. I started to follow the program on April 26, 2007 and boy has that changed my life!. I have so far lost over 65 lbs. and my energy has increased. Since I have been on this Herbalife Weight management program, I have kept off my weight and my tremors have quit and now I have been able to pick up a pencil or pen and start to take notes and write. I have not been able to do that for over 30 years and you can read it. So in Jims Corner Shop.com you will fine the products from Herbalife, and Puritan Pride that I have used that have helped me. So that is the main reason that I started my website www.jimscornershop.com. In this website You will also find some of the Hand Made Crafts that I have made as a way for me to keep my tremors manageable, other fine hand made crafts, some computer equipment, and some fishing gear for the sports men. You will also find a line of exercise equipment that you can buy and use in the comfort of your own home if you are not able to get out to a gym or if you are confined to your own home. I hope when you look through all the pages you will find something that would be of help to you. Please sign in and leave a message on what you thought of the website. Thank YOU for shopping in my website. May The Lord be with YOU the rest of YOUR DAY.
James Eckburg
www.jimscornershop.com
info@jimscornershop.com
eckburgjoe@yahoo.com
815-493-6475
114 E. Franklin St.
Lanark, Illinois 61046
http://blogfather.net/blogs/eckburgjoe.xml
