Articles on Medical Diseases and Conditions

Tag: Drugs

  • Fatigue, cognitive problems and depression: Cognitive problems

    Research has identified two broad areas where Multiple Sclerosis seems to be involved or has effects that are not so much to do with the mind in general, but with what are more neatly and technically considered as cognitive issues on the one hand, and attitudinal and emotional issues on the other.
    Cognitive issues are those that concern our thinking, memory and other skills, which we use to form and understand language; how we learn and remember things; how we process information; how we plan and carry out tasks; how we recognize objects, and how we calculate. It was thought until recently that memory loss and some other cognitive problems were a rare occurrence. However, more recent research has suggested that a range of cognitive problems varying widely in type and severity may be present in many people with MS.
    Of course people with MS, just like anyone else of a similar age and sex, can suffer mental illness or dementia but, clinically, people with MS do appear to have more depression (see next section) compared to other people, and perhaps have what might be called mood swings rather more often. More recently, studies have shown that many people with Multiple Sclerosis have some problems with memory and with what are called their cognitive abilities, and these seem to be associated with the effects of the disease. It is thought that MS could lead to a subcortical dementia but this is not inevitable. We discuss depression and mood swings later in this chapter.

    How to recognize the problem

    We can all change without necessarily realizing the nature or extent of that change – until someone tells us. Sometimes people with MS may be so depressed or anxious that they think their cognitive problems are worse than in fact they are; on the other hand, they may not want to acknowledge them at all, for they do not want to think that MS may affect their cognitive as well as their physical functions. In addition to the general variability of symptoms, an issue that we have indicated is characteristic of MS, we have also noted that previously it has been very difficult to link cognitive performance to any other aspect of MS. However, more recently, studies using MRI (magnetic resonance imaging) have shown that the more general the demyelination the more likely it is that significant cognitive problems will also exist. Moreover, MS lesions in certain areas of the brain seem to be associated with cognitive difficulties. Further work will, it is hoped, be able to identify more precisely the relationship between certain kinds of cognitive problems and areas of the brain affected by Multiple Sclerosis.
    In addition, during acute attacks of MS, it has been observed that cognitive performance – memory and concentration, for example – may get significantly worse and then improve again; on the other hand, if the cognitive problems have arisen gradually and have been present for some time, then it is unlikely that they will improve substantially.
    Family perceptions may be more accurate on occasions but, although we all suffer from memory lapses from time to time, it may be tempting for you or some family members to put down every piece of forgetfulness to the Multiple Sclerosis. To avoid possible uncertainties, concerns or perhaps even recriminations, you should seek an objective assessment of any cognitive problems, if possible with a referral to a clinical psychologist, or more specifically to a neuropsychologist – usually from your neurologist.

    Professional opinions
    Until the results of recent research, many GPs and neurologists did not consider cognitive symptoms to be a major issue in relation to MS. Because the understanding and use of language is quite good in people with MS, in a single or occasional interview or consultation, it may be hard for a doctor to pick up more subtle but still important cognitive prob- lems. As we have suggested, it is far more likely that those who are with you, and see you everyday, will notice these things first. People with MS have found that cognitive problems can be one of the main reasons why they have to go into residential care or why they become unemployed.

    Tests
    Formally, the range and extent of any cognitive problems can be measured and monitored through what are known as ‘neuropsycho- logical tests’, usually given by a psychologist. They would involve some verbal and written tests focusing on things like your memory and your ability to solve problems of various kinds. These tests are becoming more sophisticated and you may be given a group (often called a ‘battery’) of tests that could take perhaps an hour or more to do. Your performance on these tests is then compared to those of normal healthy adults, and it is assumed that, unless there are other explanations, a much lower performance on one or more tests is due to MS. These tests are only given routinely in some clinical centres at present and, because this is still one of the developing areas of research and clinical practice in MS, you may need to attend specialist centres to obtain such an assessment.
    Because some medications may affect your performance in tests, you should make the person who is testing you aware of what medication you are currently taking. The testing process itself may be problematic for other reasons. For example, many of the tests used for people with MS require a degree of coordination and manual dexterity, and this may be compromised by other ef fects of Multiple Sclerosis. Also, a problem in one area of cognition can affect performance in a test in an unrelated area, or it may be difficult to compare tests involving spoken responses with tests involving written or manual responses.

    What might affect cognition?

    Emotional state
    Your emotional state may affect your cognitive performance, but the exact relationship and mechanism is not yet clear. Some studies have shown that depression seems to be related to cognitive performance, and others have shown the opposite.

    Heat
    Heat, or getting hot, may affect your cognitive performance, as it may influence other symptoms from time to time. Although little research has been undertaken on heat and cognition, on the basis of research on other symptoms it would be reasonable to conclude that if, for example, your memory could have been affected in this way, it would be likely to return to normal with a reduction in the temperature.

    Medication
    Medication may also affect cognition, particularly those that have cen- tral nervous system effects, such as sedatives, tranquillizers, certain pain killers and some steroid treatments. You should be aware of this possi- bility while you are doing everyday tasks that require concentration.

    Cognitive problems found in Multiple Sclerosis

    We must re-emphasise that the variability of cognitive problems in MS is very wide, some people do not have any cognitive problems and in others they are very mild. However, for information, the sort of problems that research has revealed are as follows. Memory loss is the most frequently found cognitive problem in MS. This may involve problems with short- term memory – failing to remember meetings or appointments, forgetting where things are and so on. There is also some evidence that people with MS may find it harder to learn new information. There are also difficulties with what is called abstract reasoning in some people with MS – that is the capacity to work with ideas and undertake analysis or decision-making in relation to such ideas. Sometimes speed of information processing may be af fected in Multiple Sclerosis – things seem to take longer to think about and do. It may be more difficult to find words, and concentration can tend to wander more readily. In addition it is possible that capacity to organize things spatially becomes more difficult – for example putting together self-assembly furniture is more of a problem.

    Management

    Drugs
    At present there are no drugs approved and accepted for the management of such problems as memory or concentration in MS. Memory problems are, of course, not limited to people with MS, and there is considerable research in this area. However, the cause of memory problems varies between different conditions, so drugs that might be helpful for people with Alzheimer’s disease, who have very severe memory problems, would not necessarily be useful for people with MS. Nevertheless, there is increasing research to see whether a number of drugs, often originally developed for other purposes, might help people with MS.
    There is some evidence that drugs used to assist fatigue may have modest effects on some cognitive problems. There are currently trials to see whether the drug pemoline might help cognitive function, and preliminary research on amantadine has suggested that it might have some ef fect on information processing. A drug with the proprietary name of Aricept, used for the treatment of memory disorders in Alzheimer’s disease, is being studied to see whether it has any similar effects in people with MS. However, whilst in Alzheimer’s disease this drug appears to increase the availability of a substance called acetylcholine, a neurotransmitter, this does not seem to be relevant to the cognitive problems in MS.
    It is possible that beta-interferons and other recent drugs used to help manage Multiple Sclerosis itself may have some effect on cognitive function, for, as we have noted, that function tends to be more problematic the larger the number of lesions in the CNS. If the speed with which this increase is lessened, then there could be some effect on cognitive function. However, until recently, it has not been usual to include neuropsychological tests in clinical trials of such drugs, so further detailed research is needed and is now being undertaken.
    Finally there has been publicity recently about the possible use of preparations of ginkgo biloba (made from the leaves of the Ginkgo biloba tree which grows in the Far East) for problems of memory and concen- tration. Trials of ginkgo biloba in people without MS have produced mixed results, early trials being promising but a major recent trial suggesting that it has little or no effect on memory and concentration. There have been no systematic trials on people with MS as yet and so no formal evidence that it could assist with their cognitive problems. In any case there are always problems in ensuring the purity of the active ingredient in such a product, and you should be cautious about its use.
    Overall the investigation of possible drug therapies for cognitive problems is a large area of current research and it is hoped that major advances will be made in the next few years in this area.

    Professional help
    This is a very rapidly developing area of professional interest in relation to cognitive problems. Until recently, the main professions in these aspects of everyday living have been occupational and speech therapy. So, as part of the process of managing everyday activities, occupational therapy helps you to organize your environment, as well as your skills, to the maximum advantage. Speech therapy helps you with speech production problems, particularly if you take some time to articulate what you wish to say.
    Some occupational therapists, particularly in North America and now in Britain, are developing special skills to help people with their memory and cognitive problems – often described collectively as cognitive rehabilitation. This is an approach designed to try and improve the everyday functioning of people with cognitive impairments resulting not only from Multiple Sclerosis but also other central nervous system disorders, such as head injury or stroke.
    There are two broad approaches to cognitive rehabilitation. The first of these is to try to restore the lost functions, often through retraining, with the use of repetitive techniques such as learning lists, and helping people to re-acquire skills with progressively more complex tasks. The second is based on the idea that, because it will be difficult to regain the lost functions, compensatory strategies are needed, in which other devices and procedures are used, such as trying to minimize distractions, or using other means of reminding you about activities that you need to do. Both of these approaches are designed to help people manage their everyday lives better despite any cognitive impairment.
    We need to repeat that cognitive rehabilitation, as a formal programme, is not available everywhere for people with MS. At present, following assessments, you will probably have most contact with an occupational therapist, whose skills focus substantially on the abilities needed to accomplish everyday activities, but we expect that many such therapists will increasingly be using at least some of the key techniques for managing problems that you may have in the area of memory or concentration.

    Self-help
    People with MS can be affected by a range of cognitive problems, and it is difficult to advise you precisely without knowing exactly what they are.
    The difficulties often mentioned specifically – concentration and memory
    – are quite common.
    Concentration. Everyone has occasional problems concentrating on things. Sometimes the problem is that we have many things going on at the same time – television, other people talking and a whole range of other activities going on. However, for someone with MS, concentrating on one of these activities – a conversation, for example – can be quite difficult, when so much else is happening. So the key thing is to try and have only one thing going on at a time – a conversation or the television, not both at the same time. You might have to move between rooms to achieve this. Find out when and where problems for you are most difficult, and then work on reducing the distractions to the minimum. Obviously changing your pattern of normal activities to help you concentrate may not be easy, but may be preferable to having continuing concentration problems.
    Memory. There are many ways in which you can jog your memory. Some of these are routine, and may appear overpedantic or fussy for someone who has only minor memory difficulties, but all help to deal with shor t-term memory problems. For example, just making sure that clocks and watches show the right time; ensuring that today’s date is prominently displayed somewhere; having a message board to note activities for today and tomorrow; having a list of activities that you are intending to do, with times and dates, perhaps in the form of a diar y or similar record. Although this might seem almost too formal, note things down that you have agreed to do, or that you and other s think impor tant, so that it doesn’ t appear that you have forgotten it.
    If you have difficulty with reading, check with your doctor whether you have any of the several potential eye problems associated with MS, that may interfere with your ability to read. Secondly, try and find a strategy to read in a particular way to maximize your ability to retain a story line.
    As a broad guideline, the more of your senses that you use, the more likely you are to remember and retain ideas. Most people read things silently. It may be worth repeating what you read out loud, or at least key parts of it; or relate some elements of the story to another person; or write key ideas down. In this way, using more than one of your senses – writing, seeing, hearing and saying – you stand a better chance of remembering the story, or indeed other material. Admittedly, this approach may require some tolerant support from those around you but, if you are making a big ef fort to improve your memory, they will probably feel that they are gaining too.
    You may find that you do not need to go to these lengths to help your memory – you could work out the main lines of the story or newspaper article by ‘skim reading’ so that, although you may have lost the element of surprise (about the ending of a story, for example!), you will have got an overall view of the text.

  • Sensations and pain: Pain

    For many years Multiple Sclerosis was considered, medically, to be a painless disease, probably because the process of demyelination was thought in itself not to be painful. However, people with MS themselves have known for many years that specific symptoms could cause considerable pain, and this is now being recognized.
    Chronic pain is experienced by about 50% of people with Multiple Sclerosis. Although pain is more common amongst people with severe MS, and amongst older people with the disease, almost everyone will experience some kind of pain at some point.

    Trigeminal neuralgia

    Trigeminal neuralgia is a very acute knife-like pain, usually in one cheek, and sometimes over one eye, but it rarely affects both sides of the face. It is caused by the lesions of Multiple Sclerosis damaging trigeminal nerve pathways. Drug treatment usually includes carbamazepine (Tegretol), although this drug does produce side ef fects, which may be a problem. The primary side effect is sleepiness, so the drug may be started in low doses and then given in higher doses until the pain is controlled. It is also possible that phenytoin, which has a milder action than that of carbamazepine, may be used, or less commonly, baclofen, which is usually given for spasticity. Another approach is to try and block the inflammation; if this is associated with a relapse, steroid therapy is given. If there is a continual problem of trigeminal neuralgia linked to several relapses, then a prostaglandin analogue called misoprostal (Cytotec) can bring relief. In some cases, various surgical operations, including the
    ‘gamma knife’, can destroy the relevant nerve pathways. Even if the trigeminal neuralgia reappears, as it can do, then the treatment can be started again, and it will almost certainly reduce the pain.

    Jaw pain

    There are other types of pain that may affect the facial area, which may not be linked to particular forms of myelin damage: temporomandibular joint (TMJ) pain affects the jaw area, or you may get more general migraine or tension headaches. Drug therapy can help counteract this pain, but in each case will be dependent on a careful investigation of the cause of the pain, and particularly the extent to which it appears to be linked to the Multiple Sclerosis, or to something else.

    Pain from unusual posture and walking patterns

    Pain from poor posture when sitting or lying, and from unusual walking patterns, is quite common. In most cases the pain does not result from the neurological damage of MS, but from its effects on movement.
    In fact one of the most common kinds of pain treated by neurologists in relation to Multiple Sclerosis is low back pain, often arising from an abnormal sitting posture or from a way of walking that has developed as a result of damage to the control of leg muscles. This may result in a pinched nerve from ‘slipped discs’, or other back problems, which can also be caused by unusual turning or bending motions. Painful muscle spasms may also result.
    So it is important to pay careful attention to how you sit and how you move in order to lessen such difficulties. You may need to seek advice from a physiotherapist in relation to both posture and movement. Comfort may be obtained by:

    • massage of the back, if carefully undertaken
    • ultrasound
    • TENS
    • specific exercises, to relieve muscle spasms
    • drugs designed to reduce spasms, and finally
    • surgery, if there are disc problems.

    Other painful conditions, particularly painful swelling of the knee(s) or ankle(s), can result through problematic patterns of walking. You must seek careful advice in relation to these conditions. It is possible that orthopaedic doctors, recommending conventional orthopaedic exercises for such conditions, may not fully realiz e that having Multiple Sclerosis could mean that such exercises fail to work. It is likely that the swelling/pain of one joint may be easier to remedy through what is called an ‘assistive device’ (e.g. a crutch) to take the weight off a weaker leg, or a knee brace.

    Spasticity and pain

    Muscular cramps and spasms are known as ‘spasticity’. Several muscles contract simultaneously, both those assisting movement and those normally countering it. These muscles will feel very tense and inflexible – this is because what is medically called their ‘tone’ increases, and movement becomes more difficult, less smooth and possibly rather ‘jerky’.
    Spasticity is quite a common symptom in MS and is often very painful: it can occur in the calf, thigh or buttock area, as well as the arms and, occasionally, the lower back. Spasticity can lead to ‘contractures’, where the muscle shortens, making disability worse.
    There are a number of ways of managing spasticity in Multiple Sclerosis:

    • Use your muscles as much as possible in everyday activities, and undertake regular stretching exercises to help reduce muscle shortening.
    • Specific exercise recommended by a physiotherapist, such as swimming, or undertaking stretching exercises in a pool-based environment, should be done on a regular basis – an important point, as spasticity is likely to be a continuing issue.

    Devices to assist in the management of spasticity
    There are specific devices that may be useful for people with Multiple Sclerosis when spasticity occurs regularly in key muscle groups, and exercises alone do not appear to deal with the problem. There are devices to spread the fingers or toes. What are called ‘orthoses’ – in effect braces – keep the hand, wrist or foot in an appropriate position or prevent ranges of movement that may result from, or cause, spasticity. A particularly useful brace may be one that places the ankle in a good position in relation to the foot and thus lessens the possibility of local muscle contractures, as well as lessening the stress on the knee. It is important that all orthoses are specifically suitable for the individual concerned, as of course body shapes and sizes vary considerably.

    Drugs
    There are several drugs available to help muscles relax, and ensure that as few of your activities as possible are affected. It is difficult to target spasticity specifically, so some people may need medication occasionally, in the day or at night, and others may require more continuous medication. It is difficult to get the balance and the dose right, and this often has to be done on a trial and error basis.
    One of the most common and effective drugs for spasticity is baclofen (Lioresal), but it can have side effects; some people find it hard to tolerate high doses. Effective doses may vary widely for different individuals. Normally this drug is taken by mouth, but other ways of administration are being developed to help people with more severe symptoms.
    Other muscle relaxants, such as the widely used diazepam (Valium) can also be used, but they may have general sedative effects, causing drowsiness; this is why diazepam might be particularly helpful at night. People are also worried about whether they might become dependent on these drugs in the longer term.
    There are some newer drugs in the process of being introduced, which on their own, or in combination with the more established drugs, may target the spasticity more specifically:

    • Dantrolene (Dantrium) tends to reveal and possibly exacerbate any muscle weakness that may be present, and its effects should be carefully monitored.
    • Tizanidine (Zanaflex) is a relatively new drug, and may work in some cases when baclofen and other drugs do not; it can also be used in conjunction with baclofen. It produces more sedation than baclofen but less weakness.
    Some other drugs work best for specific muscle groups in the body – such as cyclobenzaprine HCl, which is useful for the back muscles, although it may work for other muscle groups as well. It can also be used in relation to another drug for spasticity.
    In relation to chronic spasms, which may result in a complete arm or leg being extended or stiff, carbamazepine may be used, although baclofen can be very helpful. Cortisone can sometimes be used to assist short-term control of such spasms – although it is not for long-term use because it has a range of side effects.
    It is possible that any or all of the drugs above may become less effective over time and thus one of the possibilities is to stop taking the drug concerned for a period of time before starting it again.
    There are other drugs undergoing trials at present in relation to the control of spasticity. One of the most promising is cannabis (or, in practice, combinations of cannabinoids – the chemical constituents of cannabis).
    There may be occasions, especially later in the course of Multiple Sclerosis, when treatment needs to be more robust to reduce very severe spasticity. This might take the form of injections, directly into the nerve or muscle concerned, with phenol or alcohol or, more recently, botulinum toxin, which damages the nerve and produces what some call a ‘nerve block’ preventing the spasticity from occurring.

    Spasticity and surgery
    Surgical intervention may be tried in relation to spasticity if other means of control fail. This can take several forms. Nerves controlling the specific muscles of the leg may be deactivated using what is called a ‘phenol motor point block’. This may make the legs more comfortable but clearly does not assist mobility. Other techniques may help spasms in the face – indeed botulinum toxin (Botox), which is increasingly being used for cosmetic purposes, may help small but very irritating facial spasms. Sometimes nerves or tendons controlling specific muscles that are producing major problems might be cut if there are no other easy means of control.
    A relatively recent development is the use of baclofen pumps to deliver the drug directly into the spinal canal to control spasticity. This process is still expensive and is what doctors would call an ‘aggressive’ treatment for spasticity, although it does allow a much finer and more detailed management of the flow of the drug.

    Pain from other Multiple Sclerosis symptoms

    Apart from the types of pain that we have already discussed, there are other sorts that can be associated with MS symptoms, such as that from:

    • urinary retention or infection;
    • pressure sores (later on in the disease), if not treated as early as they should be;
    • eye conditions, especially ‘optic neuritis’, when the optic nerve swells.

    In general, if the source of the problem is treated, the pain will disappear, although the management of the neurological causes of pain is more difficult than management of pain from other sources.