Articles on Medical Diseases and Conditions

Tag: Multiple Sclerosis

  • Multiple Sclerosis (MS)

    Multiple sclerosis is a chronic demyelinating disease that has a reputation for recurrent illness of unpredictable length and severity. A multifocal demyelinating process in cerebral hemisphere white matter results in various combinations of weakness, ataxia, vision difficulties, and parasthesias, frequently ending in paralysis. Thus, the clinical symptoms, especially early in the disease, can be mimicked by a considerable number of other conditions.

    Cerebrospinal fluid laboratory findings. Routine CSF test findings are nonspecific, and when abnormality is present, the standard CNS test results are similar to those of aseptic meningitis. The CSF total protein is increased in about 25% of cases (literature range, 13%-63%). The cell count is increased in about 30% of cases (literature range, 25%-45%), with the increase usually being mononuclear in type and relatively small in degree.

    The CSF gamma-globulin (IgG) level is increased in 60%-80% of cases (literature range, 20%-88%). Technical methods such as radial immunodiffusion produce more accurate results than electrophoresis. Problems have been recognized in interpretation of CSF gamma-globulin values because elevated serum gamma-globulin levels can diffuse into the CSF and affect values there. Many investigators analyze a specimen of serum as well as of CSF to see if the serum gamma-globulin level is increased. Several ratios have been devised to correct for or point toward peripheral blood protein contamination. The most widely used is the CSF IgG/albumin ratio. Albumin is synthesized in the liver but not in the CNS and therefore can be used to some degree as a marker for serum protein diffusion into the CSF or introduction into the CSF through traumatic lumbar puncture or intracerebral hemorrhage. The IgG/albumin ratio is based on the theory that if serum leaks or is deposited into spinal fluid, albumin and IgG will be present in roughly the same proportion that they have in serum; whereas a disproportionate elevation of IgG relative to albumin suggests actual production of the IgG within the CNS. The normal CSF IgG/albumin ratio is less than 25% (literature range, 22%-28%). About 70% of MS patients have elevated IgG/albumin ratios (literature range, 59%-90%). The IgG/albumin ratio is a little more specific for MS than increase of IgG by itself. However, many conditions produce increased IgG within the CNS, such as chronic CNS infections, brain tissue destruction, CNS vasculitis, systemic lupus erythematosus and primary Sjцgren’s syndrome involving the CNS, and various demyelinating diseases.

    Another way to estimate CNS production of IgG is the IgG index, which is (CSF IgG level/CSF albumin level) ч (serum IgG level/serum albumin level). This index is reported to be abnormal in about 85% (range, 60%-94%) of definite MS patients. A third method for estimating CNS IgG production is the IgG synthesis rate formula of Tourtellote. Sensitivity of this method is about 85% (range, 70%-96%). Consensus seems to be that the IgG index is slightly more sensitive and reproducible than the IgG synthesis rate. Both can be influenced by altered blood-brain barrier permeability or presence of blood in the CSF as well as the various conditions other than MS that induce CNS production of IgG antibody.

    Another useful test is based on the observation that patients with MS demonstrate several narrow bands (“oligoclonal bands”) in the gamma area when their spinal fluid is subjected to certain types of electrophoresis (polyacrylamide gel, high-resolution agarose, or immunofixation; ordinary cellulose acetate electrophoresis will not demonstrate the oligoclonal bands). Oligoclonal banding is present in 85%-90% of MS patients (literature range, 65%-100%. Some of this variation is due to different methods used). Similar narrow bands may be found in subacute sclerosing panencephalitis, destructive CNS lesions, CNS vasculitis, lupus or primary Sjцgren’s syndrome involving the CNS, diabetes mellitus, and the Guillain-Barrй syndrome. A similar but not identical phenomenon has been reported in some patients with aseptic meningitis.

    Antibodies have been produced against myelin components, and a radioassay for myelin basic protein (MBP) is available in some reference laboratories. The MBP level is reported to be increased in 70%-80% of patients with active MS (literature range, 62%-93%), depending to some extent on the status of active demyelination. Incidence is less if the disease is not active or if steroid therapy is being given. The various demyelinating conditions other than MS also produce abnormal MBP assay results. The MBP level may also be increased in destructive CNS lesions such as a CVA, in some patients with the Guillain-Barrй syndrome, and in some patients with CNS lupus erythematosus.

    Summary. Of the various laboratory tests for MS, the two most widely used are the spinal fluid IgG index and presence of oligoclonal bands. Of these, the best single test is probably oligoclonal banding. CT and MRI can often demonstrate focal demyelinized areas in the CNS, with CT reported to show abnormality in 40%-60% of patients with definite MS and MRI positive findings in about 90% (range, 80%-100%). Neither CT nor MRI is currently able to differentiate MS with certainty from other CNS demyelinizing diseases.

  • Research: New lines of research

    Genetic research

    Chapter 1 discusses the possible causal relationship between MS, genetics and the environment. The most striking thing now is the speed at which research on possible underlying genetic factors is being undertaken. Of course, this research is part of the massive international research effort which has now ‘mapped’ human genetic makeup – in other words which has unravelled the human ‘genome’. In the course of this research more and more genetic associations with particular diseases are being uncovered. Of particular interest is the fact that genes control the human immune system, and so, if it turns out that people with MS have a clearly different genetic makeup to other people, ultimately the most effective way to manage immune system malfunctions may be to try and deal with those genetic differences. This will not be a simple process because several genes are already known to be implicated in MS, unlike some other conditions where only one gene is involved.
    Currently genetic research on MS is based on two main lines of inquiry:

    • Genes that allow the body to recognize which are its own tissues and which are those of an ‘invader’ bacteria or virus are being studied. If this recognition process goes wrong, then an
    ‘autoimmune’ attack of the body’s own tissue is likely to occur, as in MS. The genes under investigation here that perform this recognition function – ‘histocompatibility genes’ – are usually either HLA (human leukocyte antigen) genes, or MHC (major histocompatibility) genes.
    • The genetic control of ‘lymphocytes’ (T cells), which are one important class of cells responding to insults to the immune system, is the second line of study. Although there is much detailed research still to be undertaken, it appears likely that a combination of genes controlling these lymphocytes and related immune
    activity produces a susceptibility in people with MS to the disease, although other triggering factors, perhaps environmentally determined, may be necessary for the onset of the disease.

    Research on viruses and Multiple Sclerosis

    The relationship of viruses to MS has been the subject of much research over the past two decades, and causes an equal amount of controversy. Almost every year, it has been claimed that a virus specific to the cause of MS has been discovered. However, none of these claims has been sustained after further extensive investigation. The basic issue is really one of cause or ef fect. Does a virus cause Multiple Sclerosis, or does a weakened immune system have the effect of making the body more susceptible to attack by viruses? Most researchers believe the latter to be the case, but an existing faulty recognition process in the immune system may either also fail to recognize (and thus attack) an invading virus, or such a virus may, through the same process, accelerate the body’s own attack on itself. In this respect recent work on viruses is being linked to other research on malfunctioning immune systems, and genetic research is also continuing.

    Regeneration of myelin

    This research area – trying to regenerate myelin – has been significant over the past few years. The cells that produce myelin are called
    ‘oligodendrocytes’, one of a family of what are described as ‘glial cells’. If the life of oligodendrocytes could be fully understood, as well as their role in the formation and repair of myelin, then an attempt to encourage their revitalization in MS could be made. This research process has also involved investigating exactly how the nervous system responds to myelin damage and how scar tissue is formed, as well as estimating what effects regeneration of myelin might have.
    Research on myelin damage and possible regeneration is yet another story of an initially hopeful scientific development followed by major disappointment. For some time it was thought that myelin could not be regenerated at all, and then more sophisticated techniques indicated that myelin repair did occur in Multiple Sclerosis, although it was very slow and weak – and was not enough to compensate for the original damage. Now scientists are concentrating on seeing whether and how this process of repair might be made more effective. The importance of this research is the knowledge that, even if myelin has been lost (and thus messages along the nerves are malfunctioning), the underlying nervous tissue is almost certainly still intact, at least in the early stages of MS; thus, if it was reinsulated (remyelinated), it may well be able to function normally. Once demyelination has occurred for some time this may be less likely.
    Animal models have suggested that remyelination is possible in such a way as to restore some functions originally lost. Strategies have included:

    • using substances called growth factors to enhance the actions of myelin-producing cells;
    • trying to inhibit other processes that weaken the actions of those cells, or
    • in a more adventurous way, investigating the possibility of transplanting cells to produce myelin.

    There are a number of substances being tested on humans to assist remyelination, although the lessons of the disappointments of equally promising possibilities arising from animal work with EAE (see above) are important to bear in mind. It is also important to say that most of the remyelinating strategies are essentially compensatory ones, i.e. they do not address the underlying disease process that is still going on – whilst some remyelination may be assisted, other demyelination may be occurring or about to occur. In addition for those with long-standing Multiple Sclerosis, the underlying nervous tissue will probably have been damaged, as well as the myelin coating of that tissue. In such a situation, remyelination may have little or no effect on symptoms.

  • Childbirth

    Miscarriage and relapse

    Women with Multiple Sclerosis run an increased risk of a relapse after a miscarriage as well as after delivery of a baby at the expected time. Miscarriage occurs quite commonly (about a third of all pregnancies miscarry), although many of these miscarriages occur so early in pregnancy that you may not realize what has happened. There is, however, no evidence that a larger number of pregnancies – or a large number of miscarriages – result in any worse outcome as far as MS is concerned.

    Delivery problems

    Some women with MS who have muscular weakness in their legs or lower bodies, or who may have spasms, might need some assistance with childbirth – perhaps an epidural anaesthesia, for example, or the use of forceps or even a caesarean. However, there is little evidence that MS causes major additional changes in the way that babies are delivered compared to those of women without MS.
    The general experience in relation to women with MS is that their pat- tern of delivery is no different from that of other women. The overall advice for women with MS in relation to preparing for the birth is the same for all women. Prenatal classes, run by your local midwives, and often also by the National Childbirth Trust, would be useful both for you and your partner if you have one, so that you can be taken through the stages of labour and how best to manage them. It may also be worth dis- cussing techniques of pain relief with your midwife and the obstetrician.
    There is one other point that you may need to know. If you have been taking steroids over the past few months, such as Prednisone (generic name prednisolone) – and this is one of the drugs that pregnant women have taken safely – then it is possible during the delivery that you will need an extra dose of this drug. This is because during labour the adrenal gland may be ‘overloaded’, if you have taken steroid drugs over the preceding months, and an additional dose, a ‘boost’, is needed. This issue ought to be raised with your midwife, and with the obstetrician before the delivery itself, so that they are aware of the situation.

    Breastfeeding

    If you decide not to breastfeed your baby, you can start taking your drugs again shortly after the delivery of the baby. If you decide to breastfeed, then you do need to seek your doctor’s advice – for drugs may be passed to the baby in breast milk.
    Breastfeeding is generally recognized as giving the baby the best possible food in the first few months. Of course breastfeeding is only a part of an often exhausting experience that all women have in caring for a newborn baby. If you can, arrange for someone else to help you in the first few weeks after the birth, and whilst it is important – if you wish to continue breastfeeding – to undertake all the feeding yourself in the first
    2 or 3 weeks, someone else could help with the particularly exhausting night-time feeds with previously expressed breast milk, or with a relevant formula feed.
    Just to reiterate, it is important to be very careful about drugs you are taking during breastfeeding, for they may be passed to the baby through breast milk. With the newer interferon-based drugs and copolymer (Copaxone), you must seek your doctor’s advice and you may have to consider not breastfeeding your baby, if you take these drugs.

  • Pregnancy

    Do discuss both your plans and any worries that you have with doctors, and other professional staff looking after you. Pregnancy and childbirth is a time for continuing support. You can receive good advice, and possibly information about sympathetic obstetricians, from the local branch of the Multiple Sclerosis Society or other MS support groups.
    In the past there was often very clear and very negative advice given about pregnancy to someone with MS. In general now this view has changed. A useful way to proceed is to discuss with your partner and/or family and close friends, a series of ‘What if ?’ questions, considering, for example, some of the problems that might occur financially or in relation to child care. Through these means you can rehearse some of the ways of managing potential difficulties, in the hope, and in many cases the expectation, that such problems will not occur.
    Relapses tend to be lower in number during pregnancy, and overall most women find their pregnancy is relatively uneventful from an MS point of view.

    Feeling good

    Many women with MS feel really well while pregnant and would like that feeling to continue afterwards! What is almost certainly happening is that some immunosuppression is occurring naturally in your pregnancy, and lowering the levels of Multiple Sclerosis activity. So far it has not been possible to identify any of the specific hormones or proteins produced in pregnancy that produce this ef fect, although one pregnancy hormone has been identified, which suppresses an experimental form of MS in the guinea pig. So there is some basis for optimism in this line of research. However, applying animal-based research to humans has been a notoriously fickle and unpredictable process, so it would be unwise to expect immediate developments as far as people with MS are concerned. On the other hand there is an increased risk of relapse of your MS after delivery and if you should suffer a miscarriage (see below).

    Taking drugs

    As an important general rule you should not take any drug, even an over-the-counter drug, during pregnancy, or indeed when you are considering becoming pregnant, without discussing this first with your doctor. For many drugs used to treat the everyday symptoms of MS, there is substantial information available about the consequences of their use during pregnancy, and many of them are safe to use.
    Those drugs that are now being used to treat the disease itself, rather than any one specific symptom, such as the interferon-based drugs (such as Avonex, Betaferon and Rebif) and Copaxone, are powerful immuno- suppressants, and it is still not clear what effects they will have on an unborn baby. You should stop taking such drugs once you have started trying for a baby, for it will be some time before you know you are pregnant and in the meantime the fertilized egg could be developing. It is a question of balancing your own concerns about the effects of Multiple Sclerosis on you, and the health of your unborn baby. The decision may not be an easy one to make, but most mothers treat the health of their unborn baby as their main concern at this time.

  • Finances: Managing finances

    Power of Attorney

    You may, at some point, feel the need for someone to take over your financial arrangements. If so, you will almost certainly need good legal advice, perhaps at first from Citizens Advice if you have not already got a good solicitor. Because this situations tends to happen when you get older, and some good documentation is available from Age Concern, especially their Factsheet Number 22: Legal Arrangements for Managing Financial Affairs. There are two versions, one for England and Wales and the other for Scotland. Age Concern offices will have these available.
    There are a range of options that a relative (or friend) might consider, from very limited permissions to deal with specific issues, to more all embracing powers, including what is called an Enduring Power of Attorney, which enables someone to act virtually in all respects on your behalf in financial matters. A special form is necessary for a Power of Attorney, which gives someone the right to act for you; you will need to sign it, as will your relative and a witness – usually not a family member, but someone who is independent. If, after signing, you become incapable of understanding the situation, then your relative will need to apply to the Court of Protection (part of the Supreme Court) for the Power of Attorney to be recognized, so that he or she can continue to act without your formal consent. If you cannot understand the situation and a Power of Attorney has not been obtained, your relative will have to apply to the Court of Protection (in England) requesting it to act as the
    ‘Receiver’ of your affairs.
    The complex procedures are designed to ensure that a decision to take over someone else’s financial affairs is not taken lightly. It does mean that it is far easier, and less costly, to try and deal with this problem at an early stage, when it can be done with the understanding and agreement of all parties.
    By the way, it is also important to make your Will, if you have not already done so; it becomes a complex area of law when a person has failed to make a Will, and subsequently interpretations have to be made of their wishes or intentions.

    Financially planning for a child when you have Multiple Sclerosis

    If you have not yet written a Will, you ought to do so. Consider the nature of your estate (including your house if you own one), and how best to ensure that the part of it you wish to use for your child is available, with the least taxation as is legally possible on your death. Even if you have made a Will, you may need to ensure that the process of passing on resources is as tax efficient as possible. You will almost certainly need to seek legal and financial advice. If you do not already have a solicitor, get advice first at Citizens Advice in your area.
    Another issue is whether it is sensible to transfer some of your assets at an earlier stage than your death to your child. This may have some long-term tax advantages. On the other hand it may reduce the eligibility of your child for certain state benefits both currently and in the future.
    Also, another thing to consider is whether your child is likely to be able to manage his or her own finances if you die, and you might need some arrangement whereby someone can manage the financial affairs – in the child’s interests, of course. There are a number of formal ways in which this can be organized – through the setting up of a Trust with your child as a beneficiary, for example. These considerations are invariably complex and need a detailed knowledge of the relevant legal situation; you need sound judgement about the long-term as well as the short-term financial consequences of the chosen course of action. It would be unwise to make major decisions on these issues without impartial advice.

  • Finances: Healthcare finance

    Prescriptions

    Unfortunately you are not entitled to free prescriptions just because you have Multiple Sclerosis – it is not yet included as one of the relatively few diseases or conditions for which free prescriptions are available. However, prescriptions are free if you are aged under 16 or in full-time education and aged under 19; if you are aged over 60; or if you are either pregnant, or have had a baby within the last 12 months. In these cases you need only to sign the appropriate section of the prescription form. Prescriptions are also free when you are receiving many forms of state benefit and this may also apply to your partner or dependent children.
    If you or your partner are on state benefits (specifically Income Support, Jobseeker’s Allowance, Family Credit, or Disability Working Allowance), you can also claim free prescriptions. Some prescriptions are also free for people receiving hospital care or diagnosed with very specific medical conditions not including MS itself, but including some of its possible complications such as genitourinary infections. There are also a number of other specific circumstances in which free prescriptions may be available, and these need to be checked out with your local Social Security Office.
    In some of these circumstances you will require a completed HC1, HC2 or HC3 form and certificate number. You can obtain the form from a Social Security office, NHS hospital, dentist or doctor.
    Even if you are not entitled to free prescriptions, you can save money if you need more than five items in 4 months or more than 14 items in
    12 months by using a pre-payment certificate. You will need to get an application form FP95 from a Post Office or pharmacy.

    Eye and dental care costs

    In addition to free prescriptions, most of the categories of entitlement listed above also entitle you to NHS (not private) dental care, eye tests and glasses or contact lenses. Necessary costs of travel to hospital for NHS treatment include the cost of travel for a partner or helper if you are unable to travel alone.
    Given the high costs of prescription, eye care and dental treatment, it is well worth exercising your claim to whatever qualifying benefits you are entitled, in order then to have these free treatments, even if you feel the qualifying benefit itself is of relatively little value to you.

  • Hearing problems

    Multiple Sclerosis is not known to cause significant symptoms in hearing (although there can always be the occasional exception), even if a test called an
    ‘auditory evoked response’ reveals some damage to the relevant nervous pathways. Very, very occasionally some hearing loss may occur temporarily as a result of the MS but, if your hearing loss is gradual or persistent, it needs investigating for other causes. Sometimes in order to diagnose and help problems with your speech, an audiological assessment may be carried out; however, any problems – as we have noted – are almost certainly not caused by the Multiple Sclerosis itself.

  • Speech difficulties: Voice production

    Voice production is a complicated process involving coordination between the relevant muscle groups, which in normal life (without Multiple Sclerosis or other condition af fecting voice production) we tend to take for granted. Speech problems are normally assessed by speech therapists – they need to know just where the problem lies for management:

    • Breathing: You may not be able to exhale in a slow and measured enough way needed for good speech production.
    • Phonation: You may not be able to speak loudly enough or with sufficient clarity or tone of voice.
    • Resonance: This additional quality of sound may be hampered by your palate not working properly.
    • Articulation: Your vocal movements may not be sufficiently precise to articulate sounds properly.
    • Phrasing and continuity: You may have difficulty in putting all the sounds together to produce sentences with appropriate pauses and so on.

    Sometimes speech may be ‘scanning’, which means that each syllable is pronounced as if it is a separate word. Occasionally speech may be
    ‘explosive/staccato’, where a syllable is forced out in a loud manner. Both these problems arise when Multiple Sclerosis affects the ‘cerebellum’, the part of the brain that deals with coordination.
    Each of these areas can be af fected by particular combinations of defective muscle control.
    If you can manage your level of fatigue well, and reduce or shorten the effects of exacerbations or attacks of MS, you may find that you have fewer problems with your speech. However, this will not always be the case and, of course, if the Multiple Sclerosis progresses, it is more likely that problems with speech will arise at some point.
    As far as the sound and tone of your voice is concerned, these change in any case as we grow older, which is why it is generally quite easy to recognize the voice of a child as different from that of an older person. In MS different aspects of voice production may change more quickly as the disease af fects the various muscles of the face, mouth and throat in different ways. Because of the damage to muscle control, your voice may be more difficult to control – it may sound high or low quite suddenly, or your speech may not sound very smooth, or perhaps you may lose your voice in mid-sentence. These problems are mainly caused by the varying, and sometimes sudden, changes in the way that your nervous system is transmitting messages to this sophisticated and normally coordinated system of voice production. There is little that can be done for the neurological difficulty itself. It is mainly a question of being aware of the problems that you have, as well as pacing your speech, and exercising the muscles to try and retain their maximum use for as long as possible.

  • Mobility and managing everyday life: Professional help

    Although there has been an explosion of health and fitness clubs, which might be thought to help people with mobility or other similar difficulties, very few of them have staff who will be aware of Multiple Sclerosis and its effects on movement. So it’s a good idea to seek the help of members of the key profession dealing with mobility and movement problems, and that is physiotherapy. Normally you will be referred for a consultation with a physiotherapist by your neurologist or GP. Check, either with your referring doctor or with the physiotherapist, that they have had experience of managing people with Multiple Sclerosis.
    A physiotherapist will normally undertake a number of assessments of your movement ability. These would include generally:

    • evaluating your general posture and body movements;
    • taking account not only of what you can do in the clinic, surgery or hospital, but also what problems you may have in and around the home and work;
    • measuring the strength of various muscles, as well as assessing how flexible your joints, tendons and muscles are;
    • testing the sensations that you may have in or around your muscles, as well as your ability to sense cold and heat.

    Some physiotherapists, particularly in leading hospitals, may undertake what is called ‘gait analysis’, i.e. a formal assessment of how you move, particularly how you walk, investigating things like speed, rhythm of movement, stride and step length. This analysis helps to determine exactly where your movement problems lie in order to help correct them. Physiotherapists increasingly like to know about your own history and your worries about your movement problems, and to try and work with them, as well as with those problems that they have detected themselves.

  • Mobility and managing everyday life

    Mobility or movement problems can be variable depending on the overall disease development, and on whether you are currently in the middle of an attack or in remission. The main aim is to maintain as much mobility as possible, in particular to avoid what might be called ‘secondary’ damage in the form of wasting (‘atrophied’) muscles, which occurs as a result of prolonged lack of use.
    In the early stages of MS, movement problems may be relatively limited or infrequent, and indeed many people find that they can continue physically with almost all the things that they did before. You may have sometimes to temper or reduce the more vigorous of your activities. As long as you are relatively active, are sensible in relation to the overall approach to exercise, and do not appear to have significant individual problems of movement, you may not need professional help or support at this stage. Do talk the situation over with your neurologist or, failing that, your GP, both of whom can refer you to professional help if they feel it necessary. Sometimes movement problems can creep up on you and, without realizing it (or perhaps not wanting to realize it), you may need more help than you first thought. In general, exercise is best thought of as a preventative process, not so much a curative one, so it is best undertaken at an early stage.