COMPLICATIONS

TREATMENT OF MS COMPLICATIONS

MS is a chronic disease and for the time being, there is no cure. MS is both inflammatory and degenerative disease, and even primary progressive type of MS could be in the beginning a case of severe inflammatory stage lead very quickly to significant degeneration lead to physical, psychological, and mental complications.

The basic rule for any illness is “protection better than cure”. This means, we must do every thing at our disposal to prevent the degenerative stage, or to halt it at a given level. 

Once complications happen, it is very difficult for the time being – apart from very few exceptions – to reverse them. The best way to prevent complications or to lessen them is by close watching and assessment of patients with MS. To treat relapses when they happen, and to treat them properly. To reduce the physical and the mental burden on sufferers by using every possible means to help these patients. The best way to manage MS in my view is by adopting a multidisciplinary team approach.

FATIGUE

The commonest complication of MS is fatigue. Between 95-98% of patients with MS suffer from fatigue at any time of their MS course.

Fatigue in MS is different from all other forms of fatigue, and it has its own characteristics and features which are some times only understood by MS patients themselves.

We – doctors & therapists – can only try our best to appreciate the real impacts of fatigue on patients with MS.

I will try to mention something about fatigue to the best of my knowledge and understanding as I am dealing with this problem for more than 14 years, and I was involved in MS fatigue research few years back.

To explain why fatigue is so common in MS, and why it is different from all other forms of fatigue including chronic fatigue syndrome (CFS) let me return back to the theory of electrical transmission within the nervous system.

We know by now that every thing we do is done via electrical impulse stimulation. Electricity is produced in body cells including of course brain cells (neurons).

Neurons are large cells and they do posses inside them very large nuclei. They produce large amounts of electricity relative to other body cells. 

Myelinated nerve fiber, and how electricity passes through
Myelinated nerve fiber, and how electricity passes through

The produced electricity has to be transmitted through myelinated nerve fibers. The electrical transmission in the myelin sheath is much faster than it is in the axon (nerve fiber). Some people think about 10-20 fold faster !. Any damage in the myelin sheath will obviously affect the electrical transmission hence, slowness of electrical transmission which leads to fatigue, exhaustion, slow thinking, and more weakness. 

 Despite of the fact that, fatigue is the commonest complication of MS, and in spite of it being so disabling; still we don’t have a single licensed drug for fatigue.

Amantadine, Modafinil, Aspirin, and Methylphenidate are used to treat fatigue in MS, albeit out of license !.

  1. Amantadine:  Amantadine was approved by the U.S. Food and Drug Administration in October 1966 as a prophylactic agent against Asian influenza and eventually received approval for the treatment of Influenza virus type A  in adults. In 1969, the drug was also discovered by accident to help reduce symptoms of Parkinson’s disease, drug-induced extrapyramidal syndromes, and akathisis. Amantadine Has been used in treating fatigue in MS, and showed some benefites in some patients. Amantadine is used 10mg daily or 100mg twice daily, the second dose to be given at or just after lunch in order for it not to disturb sleeping at night.
  2. Modafinil: Is a stimulant drug licensed for Narcolepsy (irrepressible urge to sleep especially during the day time), but in one or two studies was found to be helpful in fatigue, but other studies showed that it is not superior to placebo or antidepressant medications. It is used orally, and the starting dose in MS is 100mg in the morning. That dose can be increased to 100mg twice daily, the second dose at lunch time, but not later. Armodafinil is another similar drug which is also used in fatigue.
  3. Aspirin: Aspirin has been used to treat fatigue in MS in a controlled crossover blind study, and it has proved superior to placebo and similar to Amantadine. The used dose of Aspirin in this study was 500mg daily. Aspirin up to 1300mg in divided doses was also used. Aspirin of course has its own complications, and gastric erosions is probably the best to remember Aspirin with.
  4. Methylphenidate: Methylphenidate is a central nervous system stimulant. It affects chemicals in the brain and nerves that contribute to hyperactivity and impulse control.  Methylphenidate is used to treat attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and narcolepsy. It has been found helpful in MS fatigue in some patients.
  5. Other medications and measures: SSRI antidepressants such as Citalopram or fluoxetine, Low dose Naltrexone (LDN), Hypebaric oxygen, psychotherapy, change work style, good sleep at night, avoidance of heat and humidity, many short breaks between jobs. All of these measure may help fatigue in MS.
  6.  Hyperbaric oxygen chambers, or oxygen cylinders at home.

    BLADDER PROBLEMS

    The second commonest complication of MS. 

    Let me first review with you basic information about the urinary bladder. 

    The urinary bladder structure. It is sophisticated, and obviously more complicated than what we probably thought.
    The urinary bladder structure. It is sophisticated, and obviously more complicated than what we probably thought.

    The brain tells the bladder and bowel what to do by sending electrical signals to the muscles in the pelvic floor, the sphincters, the urethra as well as the bladder and rectal area.

    The messages or impulses sent by the brain to the pelvic area are carried by a system of special nerve fibers. These signals start in brain, go through the spinal cord and continue to the nerves located in the sacral area of the back before being sent to the pelvic area.

    Innervation of the urinary bladder in simplified way
    Innervation of the urinary bladder in simplified way .

    The bladder innervation can be divided into 3 groups:

    1- Central: originated at the cap of the pons in the brain stem.

    2- Afferent from pons to the sympathetic fibers in the thoracic spine, then to the parasympathetic nerve fibers via the sacral roots S2, S3, & S4) to the bladder smooth muscles.

    3- Somatic nerve via pudendal nerve fiber to the external sphincter of the bladder which is a striated muscle .

    The act of urination (micturition) can be summarised into the following:

    1. Urine is made in the kidneys
    2. Urine is stored in the bladder
    3. The sphincter muscles relax
    4. The bladder muscle (detrusor) contracts
    5. The bladder is emptied through the urethra and urine is removed from the body.

    The wall bladder contractions and the relaxation of the bladder and internal external sphincters are very much synchronized i.e coordinated. Any disturbance of that coordination causes problems in the bladder functions.

    How the urinary bladder is affected by MS?

    Knowing that the center of the bladder control is in the “pons”, and that the pons is the part of the brain which is the most frequently affected by demyelination in MS. Hence, we can realise easily why the urinary bladder disorders in MS are so frqent.

    Urinary bladder dysfunctions in MS can be summarised under 4 categories:

    1. Urgency: Because of unplanned stimulation of the bladder wall (the detrusal muscles) by excessive discharges from an irritated central command(pons) due to inflammation, the bladder wall naturally responds to the stimulation by irritating the bladder wall muscles forcing them to contract inappropriately leading to an urge to empty the bladder. Emptying of the bladder is immature (weak contraction) and inappropriate(no syncracy) and that results in painful, partial, frequent, and unplanned temptations to empty the bladder.
    2. Incontinence: Because of the lack of syncracy between bladder wall and the bladder out-flow orifice, the bladder control is lost and that leads to the leakage of urine in the wrong time, and this is called “incontinence”.
    3. Retention: Again, because of the lack of syncracy and the stimulation of the bladder wall at the wrong time; bladder wall contractions will be weak against a tightened external sphincter leading to incomplete emptying of the bladder and this will lead to a gradual increasing of the residual urine volume inside the bladder(post-void volume) and this will lead to increased urinary frequency and urinary retention on occasions.
    4. Infection: Urine is not entirely sterile, but normally the number of bugs in the urine are that small for not to cause any problems(infection). Bacteria loves calm(stagnant) water to grow faster, and that leads to recurrent urinary tract infections. 

    How the bladder complications in patients with MS are treated?

    1. Reduce central stimulation, by treating inflammation(relapses).
    2. Calm down the bladder wall agitations, by using anticholinergic(antimuscarinic) drugs such as: Oxybutinin, Tolterodine, Flavoxate, Propeverine, Solifenacin, and Trospium. Anticholinergic are used to treat urgency, frequency, and incontinence by reducing involuntary bladder contractions and increase bladder capacity. A Cochrane review have suggested that there is insufficient evidence to support the use of anticholinergic drugs to treat urinary symptoms in patients with multiple sclerosis (MS). Anticholinergic druds do have a lot of side effects such as: Dry mouth and eyes, blurred vision, confusion, constipation, and urinary retention. Also, anticholinergic drugs may worsen memory in MS. Other drugs which may help in this area especially incontinence are alpha stimulants such as midodrine, and pseudoephidrine. Alpha stimulants can some times develop very bad side effects such as blood pressure disturbance including postural hypotension, insomnia, worsen glaucoma and diabetic control.
    3.   Treating night incontinence by using Desmopressin, Amitriptyline, and Duloxetine.
    4. Treating recurrent urinary bladder infections by using antibiotics for acute infections and prevention of future infections.
    5. Bladder wall relaxation by using Botox Injections.
    6. Relieving bladder retention by intermittent slef-catheterisations.
    7. Treating incontinence in men by wearing penile sheaths(convenes).
    8. Permanent catheters for retention and frequent incontinence such as indwelling catheters and supra-pubic catheters.

    Note: It has been published in 2009 that Percutaneous Tibial

    No I can get some time for myself. I don't need to rush to the loo anymore !.
    Now I can get some time for myself. I don’t need to rush to the loo anymore !.

    Nerve Stimulation was effective in Overactive Bladder, and can be considered a relatively safe option in managing this MS frequent complication.

    More needed details will be written here soon !.

     MUSCLE RELATED COMPLICATIONS

    These complications likely to rank the third commonest complications of MS.

    Spasticity: Muscle spasm with related complications such as pain, cramps, jerkiness, clonus, and scissoring.

    There are two types of muscle spasm:

    A- Constant spasm: which is treated with muscle relaxants. The available muscle relaxants include:

    1. Benzodiazepines: Such as Tizanidine, and Clonazepam.
    2. Baclofen, and Methocarbamol
    3. Dantrolene.
    4. Botulinum Injections: Such as Botox, Xeomin, Dysport, and Neuroblock.
    5. Cannabinoids : Such as Sativex spray. 
    6. Intra-thecal baclofen infusion.

    Combination treatment can be considered using 3-4 of these remedies together. They do enhance one another if used properly.

     B- Intermittent spasm: Also, called phasic spasm. Some neurologists consider this type of spasm distinct to the constant spasm in many ways including its pathophysiology. Best treatment for intermittent spasm is by using clonazepam or botulinum injections in selected muscles.

    Muscle spasm of any type can be associated with pain and cramps as mentioned above. Medications used for nerve pain (Neuropathic pain medications) can also help to relax the muscles and can help the two types of spasm.

    Physical measures are very important in the management of muscle spasm such as physiotherapy, massage, acupuncture, swimming.

    DEPRESSION

    In general, depression is a frequent complication of any chronic disease.  MS is a chronic (life-long) disease for the time being at least.  Hence, no surprising at all that depression is a frequent complication of MS.

    Depression is the product of unresolved conflict because of frustration. Frequent problems and limitations lead to anxiety and frustrations. Recurrent frustrations lead to even more anxiety, anger, bad performance, and yet more frustrations. It is a vicious circle, and once any patient finds self in that vicious circle, getting out of it becomes even more difficult.

    Nearly 50% of patients with MS do suffer from a significant depression. That is out of known statistics, but the realty is different. Depression in MS in practical terms can be up to 85% among sufferers with MS. The 35% difference is explained by “denial”. Denied depression is even more difficult to treat, and can be more devastating on the sufferers’ life than the admitted one. It can be so difficult for a neurologist (sometimes the neuro-psychologist as well) to identify depression because of patient’s denial. After hard work, we may identify the denied depression, but patients usually refuse treatment because they don’t accept the diagnosis.

    One important message to all patients with MS. Depression in MS is not madness, is not a real psychological illness. Patient’s with MS depression can be different from those known with depression as a psychological illness. MS depression can be temporary and can be treated completely. When we mention the word depression to our dear patients, I don’t want them to get angry or think of themselves “mad” please. Depression is usually hide behind anxiety, fear, worry, apprehension, lack of motivation and the urge or interest to do things. Anxiety hidden behind depression can some times be responsible for the amount of pain some patients are suffering from, which is usually “everywhere”, and may not respond to pain medications including morphine preparations. If any MS patient suffered from generalised pains and takes a lot of medications (usually a combination of nerve pain and non-nerve pain) with no benefit or lack of tolerance of many pain killers, then anxiety related pains must be considered by us(neurologists) neuro-rehabilitation teams, and pain specialists… we all need to consider asking for help from our colleagues neuro-psychologists who can help us quite a lot in this area. 

    Why Depression is so frequent in patients with MS? 

    To answer such a question, which I think is a good question, and we (neurologists) need always to answer this question for ourselves first, and for our patients and their close relatives. We need to be aware of this possibility and we need to be well informed about depression in MS.

    MS in general is a disease of young females, and here I am talking about young ladies in their early twenties, who are in the beginning of their career, and in the beginning of their adult life by all its requirements i.e love, courting, marriage, children, holidays, etc. Most of sufferers with MS when they are first diagnosed do belong to the middle class of their societies. They are clever, motivated, optimistic, and dreaming of a bright future.  They are very badly disappointed on two occasions: when we tell them about the diagnosis despite of us being very professional and sensitive in telling them about it. The second occasion when young patients with MS in particular get the big shock when they started to feel the impact of MS complications such as fatigue, pain, weakness, and memory problems. They can be blamed for their symptoms rather than their illness by members of their families, their spouses, their colleagues at work, and their bosses. That sort of misunderstanding can be a strong factor for frustrations and that on itself can be a culprit for depression.

    MS is a big obstacle (ramp) lies between people and their life interests. Hence, the MS burden on people’s life is so heavy and so devastating especially for some. 

    MS also negatively affects love and marriage life. Probably the highest separation/divorce rate is among patients with MS in comparison to other diseases. Most of other neurological diseases affect people in later time of their lives, when couples tend to stick with each other with or without illness. People in their sixties or beyond tend to stick to each other whatever the situation, because each one of them needs the other almost the same way.

    Symptoms of depression

    The symptoms of depression are many and can be individualized sometimes depending on the individuals circumstances. There are 10 common symptoms which are used by  the international body to make a diagnosis of depression, what is known as: International Classification of Diseases (ICD-10). Those symptoms are summarized in the following:

    • low mood and feeling sad.
    • less energy and feeling less able to do things.
    • losing interest in activities you used to enjoy.
    • loss of concentration.
    • becoming tired easily.
    • sleeping and eating less.
    • feeling less good about yourself (loss of confidence).
    • feeling guilty or worthless.
    • losing interest in sex.
    • thoughts of self-harm or suicide, and making suicide attempts.

    Treatment of depression in MS

    The first step towards treating depression in MS is to recognize it, especially among the “denials”. The next step is to convince sufferers to accept the diagnosis and to start dealing with it. I have mentioned “dealing” with it instead of “treating” it for a purpose.

    In my view, the best professional to manage depression in MS is the patient’s neurologist. Patient’s neurologist is the professional who most frequently see the patient. The relationship between the patient and his/her neurologist is expected to be – and must be – the best relationship between a patient and a professional. A neurologist must know a lot about his/her patient, and must be the most confidant to the patient. An MS sufferer is expected to trust his/her neurologist the most, and that sort of environment must be provided by the neurologist by being understanding, good listening, respecting, and caring for his/her MS patients in particular knowing how fragile some patients would be.

    In my view, neurologists must all have some training and experience in human psychology. The treatment of depression in MS is not medical, but supportive. The best professional to treat depression in MS is an experienced psychologist, but not a psychiatrist… with my full respect for both of them.

    In my view as a clinical neurologist, the fist step to manage depression in MS must follow these lines of thinking:

    1. A neurologist must be up to date with “every thing” about MS.
    2. A neurologist must be fully aware of his patients MS.
    3. A neurologist must listen to his patient. We must allocate enough time at any other time even if it is on expense of our lunch or break time to listen to everything you patient wanted to tell you about.
    4. A neurologist must explain to his patients about his/her MS in full details including showing them their MRI images with good explanation. Other available results would have more impact on patients if they see them on computer or printed paper.
    5. A neurologist must let his/her patients to ask questions about their illness, and any other related matters. If they don’t ask questions, we must encourage them, or lead them to ask questions.
    6. When it comes to depression and any other psychological (functional  issues, I would think one-to-one approaches can be more informative to the neurologist, and more receptive and persuasive to the patient. Following a one-to-one session or sessions, two-to-one sessions must then follow, involving the spouse, guardian, carer, or a close friend with patients choice or permission.
    7. I think multidisciplinary approach can be considered for selected patients with their permission or choice. Group therapy can be considered, but not when gathering personal information from the patient.
    8. Confidentiality must be guaranteed by the neurologist, and must be felt and appreciated by the patient.
    9. Full trust and security must be a common factor between the neurologist and the patient.
    10. Patient’s respect, integrity, and dignity must be observed and guaranteed by the neurologist. 

    We need to keep in mind that all our MS patients who suffer from depression are anxious, worried, lack confidence in themselves, mostly see their failures but not their successes. Depressed patients in general see themselves as impotent and unable to perform or impress.

    The first step in my view to help our MS patients with depression is to correct for them any false believes about their illness. Any false theories in their minds, any exaggerated fears about the future.

    The next step is to show them ways (practical and possible) on how to build up confidence in their ability to do things, and to do them well. Without building up confidence in themselves they wont one step further.

    The next step is to help them sleep better and enough at night, by giving them ideas for better natural sleep without the need of sleeping pills whenever possible.

    The next step is for patients to change their life style. This is very important, and can be decisive sometimes. Their neurologist can help them chose a different lifestyle with advises, suggestions, and more information.

    Finally, let them chose targets with given times, and see them again to check on them.

    Sometimes, a combined psychotherapy with a small dose of antidepressants is required, at least for a trial period not more than 6 months.

    If all fails, then referral to a good neuro-psychologist becomes a complementary if not a necessity.

     MEMORY

    Memory in MS is a little complicated area. The memory production is a neuronal function, and neurons are concentrated in the gray matter. MS is a white matter disease in principle.

    Hence, I can easily mention that memory production in MS should be normal, and the memory  transmission is the part of memory affected.

    If we compare MS with any form of primary dementia such as Alzheimer’s disease, the the difference is significant in every aspect. Memory production in Alzheimer’s disease is principally affected, and the memory transmission in Alzheimer’s disease is generally  intact.

    There are on  these days a lot of talk about gray matter disease in MS. I thought initially and I have argued a lot that, what we see in the gray matter of changes are demyelinating changes in the axons of those neurons lying high in the cerebral cortex, but not the neurons themselves.

    I have heard a lot of enthusiasts who argued that post-mortem histopathology has shown pathological changes in the neurons, and similar was found in the tissue biopsy of alive MS patients. I still find it difficult to accept, and I will keep my thinking about memory in MS as a problem of transmission but not production…. and this is very good for MS patients.

    What supports my thinking is that memory clinics are reluctant to treat memory deficits in MS and Cholinergic drugs such as memantine and aricept are not helpful in patients with MS, because previous research failed to show any significant improvement in this group of patients with memory deficits.

    One important factor I think we need to keep in mind when talking about memory changes in MS. This disease as we know is a progressive disease, and currently all medications used for treating MS under the umbrella of DMT are not used to stop the progression of the disease let alone reversing it. MS will continue to progress what ever we treat it with. 

    The accumulation of the demyelinating plaques and the atrophied axons would only increase in size and occupy more spaces in the brain. Naturally most of those deposited plaques are concentrated in the white matter, but some will no doubt point towards the gray matter and cause a pressure effect on neurons, and this would damage neurons affecting their primary functions including memory production and other cognitive functions.

    This means that over time, there will be some progressive primary memory deficits and that can lead to real dementia in the later stages of the disease. That would be irreversible.

    How to manage memory deficits in MS?

    Currently, there are no available medications for memory deficits in MS. The memory management is then supportive and complementary.

    Every MS patient has life style, and in each one’s life style there  are things those could be modified or changed: 

  7. Food, physical activities, sleep pattern, stress, anxieties, and many things on mind. All of these factors can be modified or changed with good advises from an interested neurologist or enthusiastic neuropsychlogist, a counsellor, occupational therapist, or all.
  8. Fatigue and sleep patterns: Theses also can be modified or improved.
     
  9. Depression and related anxiety need to be treated or sorted out.
  10. Busy life: Doing one thing at a time.
  11. Memory aids: Wring down, repeat and recite, mnemonics, link names and numbers to familiar names and numbers, etc. 

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An attempt to understand around us via pondering inside us