TREATMENT OF COGNITIVE IMPAIRMENT, DEPRESSION, FATIGUE AND BLADDER DYSFUNCTION IN PATIENTS WITH MULTIPLE SCLEROSIS

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1 TREATMENT OF COGNITIVE IMPAIRMENT, DEPRESSION, FATIGUE AND BLADDER DYSFUNCTION IN PATIENTS WITH MULTIPLE SCLEROSIS Y. Dokova, I. Milanov Key words: Multiple sclerosis, cognitive impairment, depression, fatigue, disability. Adress for correspondence: Y. Dokova, SHATNP Sv. Naum, 1 Ljuben Russev St., Sofia 1113, III-rd Neurological Department, jdokova@abv.bg Abstract: Multiple sclerosis (MS) is an autoimmune, inflammatory demyelinating disease of the central nervous system (CNS), and leads to disability among young people. A great number of symptomatic problems can be observed in MS patients, such as cognitive dysfunction, depression, fatigue, mood disorders, that can lead to seriously impaired quality of life. Some other symptoms such as spasticity, tremor, seizures, sexual and sphincter dysfunctions can also lead to a progression of the disease. This paper reviews the management of these problems, because they are extremely important for the well-being of the patients. Review Article Dementia is not a characteristic for Multiple sclerosis and can be seen in less than 5% of the patients with MS. It is presented in the late phases of the disease, as well as in patients with higher disability. It has been found that 34-65% of all patients with MS have different degrees of cognitive impairment, which is determined through special neuropsychological questionnaires 1,19. Cortical syndromes such as aphasia, apraxia and agnosia, however, are not typical for MS patients. Cognitive dysfunction may be present even in the early stages of the disease. The most common impairments are connected with abstract thinking, short-term memory, attention and the speed of processing information. The course of the disease determines the variety of cognitive dysfunctions among patients 2. MS patients with relapsing-remitting (RR) course of the disease have better preserved cognitive abilities in comparison to those with secondary-progressive (SP) course of the disease 15. It is shown that the degree of cognitive dysfunction correlates to a great extent with the degree of cerebral pathology found on Magnetic Resonance Imaging (MRI). In addition, on T1-imaging on MRI the size of cortical atrophy corresponds to the degree of found cognitive deficiency 20,21. That means that lesions in the white as well as in the grey matter of the brain may be responsible for this kind of pathology among MS patients. Using neuropsychological batteries for detecting such dysfunctions in everyday practice is valuable to specialists for registering problems both, in MS patients with RR and SP course of the disease. These dysfunctions are related to the MRI findings 10. Another problem that can influence negatively cognition is the depression 3. It can seriously affect memory, attention and concentration. The relation between depression, lack of social support and cognitive impairment, no matter of the degree of physical disability, is proven. Besides, depression defines a lower level of coping with everyday life among patients with MS 4,5. These relations are very difficult to explain and treat. All patients with MS may suffer from serious clinical depression, which could lower their neuropsychological 16

2 J Clin Med. 2009; 2(3):16-21 domains. Such correlation is proven in healthy controls as well as in patients with a potential risk for cognitive impairment such as brain trauma. In MS patients, a great number of domains are affected. They are connected to executive functions and can be very delicate in moments of depression. These spheres are usually: the working capacity, the ability to plan and the speed of processing information. Depression has greatest influence on cognition in MS patients. This leads to a decline in their abilities to take decisions and to act in real life situations 8. These are situations in which healthy persons should be flexible and in which they could change according to the conditions, but they however, are very difficult for MS patients 12. The symptomatic treatment of cognitive impairment is still experimental, but with a hope to delay the processes of cognitive decline. Some studies investigated the effect of Pemoline, Amantadine and 4-aminopyridine and showed no significant effect upon cognition 11,17. More promising are the results from trials of disease modifying drugs and cholinesterase inhibitors. The treatment of some additional syndromes, such as depression and pain, can improve to a great extent the cognition and general status of MS patients 9. The progression of the cognitive decline is proven to be slowed down by some widely used disease modifying drugs. Intramuscular interferon beta 1-a (Avonex), as well as interferon beta 1-b (Betaseron) affect positively this domain. Interferon beta 1b has good effect on the visual memory of patients with relapsing-remitting MS. Applying the intramuscular interferon beta 1-a shows very good results on cognition, according to a vast study with large number of patients with RR course of MS disease 16. A twoyear follow-up of these patients has shown greater preservation of cognitive functions in main spheres like memory, executive functions and processing of information 24. The data about Rebif s effect on cognition are not proven and show no significant results. A relatively small, non-randomized, open-label study has shown a significant improvement of cognitive dysfunction in result of cholinesterase inhibitors application. It is proven that Donepezil 10mg daily leads to a significant improvement of memory in patients with MS, when that function was being followed. The patients treated with Donepezil showed better results in comparison to the placebo group. There are, however, no large long-term trials yet, to trace the results from such a therapy in the long run. A lot of non-pharmacological methods exist for treating cognitive decline in MS patients. They consist mainly of providing support and improving abilities to cope in life situations. In this aspect it seems really important that the patient himself/herself participated actively in coping with and compensating problems, as well as their solutions. For this purpose, help is absolutely necessary from the family, relatives, friends, colleagues and caregivers who should help the patients cope with everyday problems. This is not always possible and is difficult to perform for a long period of time. There is a number of strategies that may be used to overcome problems, related to cognition. These may be: Firstly, hold of personal organizers with alarms, to signalize whenever needed and useful to patients with memory problems or inability to organize daily activities. Secondly, abstention from activities which lead to physical and mental fatigue. Use of telecommunication facilities and distribution of work is important for MS patients to avoid overload and fatigue. That could help them maintain good working capacity during the whole day. Another method for overcoming cognitive problems is cognitive rehabilitation. There are, however, not enough data about the application of this method. The results from a relatively small trial showed improved quality of life in MS patients, but they are not detailed enough as to the effects on the cognitive spheres. Full and detailed studies are needed to evaluate the benefit from this method. A number of studies have shown different degrees of interference in the emotional domain in MS patients. The most common manifestation is depression. To some extent, this is due to the fact that the patient himself has to cope with his/ her chronic, incurable disease and to live with that thought. Euphoria is another dysfunction, usually associated with moderate or relatively severe degree of mental disorder. Such patients can manifest dysphoric condition with variations from depression to unfounded elation. 17

3 Depression is more common and more manifest in MS patients in comparison to patients with other chronic diseases. In addition, the suicidal risk is higher than in the general population. MS patients have lower expectations from life. Depression can negatively influence cognition as a whole. It is still unknown if depression in MS patients has a co-morbid relation to bipolar disease or is a result from lesions in the frontal and subcortical white matter. Some studies show the benefit from applying interferons to decrease depression or to prevent from developing such. Treatment of depression is mandatory and in most cases it is efficient. There are studies, however, that show that in the course of interferon therapy patients may develop depressive symptoms. In addition, pharmacological methods and psychotherapy are implemented. Another characteristic for MS symptom is fatigue. It is observed in nearly 78% of the MS patients. It is usually described as physical exhaustion, not correspondent to the quantity of work or activity performed. It seems that there is a relation between fatigue and some sleep disorders that may be detected in those patients. Typical feature is that fatigue is usually present in the very early hours of the day and intensifies till the evening. Many of the patients complain from exhaustion since the very awakening 6. Such patients respond positively to any type of treatment 23. Fatigue may be present when a relapse occurs or can precede neurological signs. It may be present long time after complaints fade. There is weak correlation between fatigue and the gravity of symptoms, as well as between fatigue and the degree of physical disability. A lot of problems connected with MS exist, which may also provoke and worsen fatigue. Many are curable: 1. Sleep disorders secondary to muscle spasms or bowel and bladder dysfunctions. 2. Depression 3. Restriction of movements. Other curable problems causing fatigue in MS patients are: 1. Anemia. 2. Thyroid dysfunction and chronic thyroid infection. 3. Sleep apnea. The medications used are antihistamine drugs, anti-inflammatory drugs, antihypertensive drugs, muscle relaxants and antidiabetic therapy 18. There are a number of medications used to treat fatigue. Such for example, is Amantadine 100 mg twice daily. It has relatively few side effects and is well tolerated by the patients. It should be avoided, however, in patients with renal insufficiency or with epileptic seizures. When the results from the treatment with Amantadine are unsatisfactory, Pemoline is used instead. Starting dose is mg twice daily and may be increased to a maximum dose of mg, or a total of 6 tablets. It is not a medication of first choice, because it may provoke liver failure. Some MS patients react favorably also to Methylphenidate in dose from 10 to 60 mg daily, in two or three applications. Selective serotonin reuptake inhibitors (SSRIs) may be used to treat depression, as well as fatigue in MS patients. The therapy may start with Fluoxetine from 10 to 20 mg daily. Another drug used often is Modafinil 22. It is used to treat narcolepsy, but it has been found that it can positively affect fatigue in MS patients. It is however, much more expensive than the medicines listed above. Another significant problem in MS patients is the bowel/bladder disorders and sexual dysfunction. Nearly 50% of all ill with MS are sexually not active, which may be a result from the disease, and 25% are with diminished sexual desire. This dysfunction may be due to lesions that affect pyramidal and sensory pathways in the spinal cord, or other psychological factors, including outer appearance, self-esteem, or rejection from the partner. This problem can additionally be intensified by other symptoms such as spasticity, paraparesis and incontinentia 7. Men have different degrees of erectile dysfunction, usually with fast loss of erection, while most women preserve their orgasmic 18

4 J Clin Med. 2009; 2(3):16-21 ability, even when there are bladder dysfunctions. Bowel/bladder dysfunction is a frequent problem in MS patients. The degree of sphincter dysfunction often corresponds to the degree of disability on lower extremities. The most common complaint is the sudden urge to urinate. Usually this is a result from depressed detrusor contractile function, which is due to suprasegmental lesion. Incontinence of urinary function in MS usually develops with progression of the disease, when the sacral segments of the spinal cord are affected, thus causing symptoms of lower activity of the bladder, which leads to less urine, interruption of the act of micturition and partial emptying of the bladder. Atonic, dilated sphincter, which empties when filled to capacity, is a result of loss of perception for bladder fullness. This, respectively, may be connected with urethral, anal and genital hypoesthesia, as well as sensor deficit of the sacral dermatomes. A study of the subjective complaints of 297 MS patients shows that there is an objective quantity of residual urine left in the bladder. It is necessary to exclude any other causes for urinating urge and incontinence. Infections of the urinary tract in MS patients are common, especially among female MS patients, and can contribute to the degree of dysfunction of the bladder 13. Constipation is more common than fecal incontinence. In a study of 221 patients with MS, 29% were with incontinence, 54% were with constipation. These problems may be a result of the upper and lower motor neuron disability in combination with decreased physical mobility. Treatment of bladder and bowel disability includes a combination of medicines depressing the urge for urination and effective urinary drainage. The medications of first choice are anticholinesterase drugs, though other drugs are studied as well. Almost all patients with paraplegia need to move regularly to improve the function of the bladder 25. Such patients are advised to reduce the quantity of liquids taken. Medication of first choice for bladder dysfunction is Oxibutinine (Ditropan), prescribed in dosages from 2.5 to 5 mg once to three times daily. Tolterodin (Detrol) is also a drug of first choice, prescribed in a dose of 2 mg twice daily, and is suitable for a long time treatment. Periodic physiotherapy and rehabilitation courses can improve the mobility of MS patients. Such may also have positive effect on the mood and the general condition of MS patients, even if the effect is short. 19

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