Psychiatric issues in multiple sclerosis.

MDD and anxiety disorders are highly prevalent among persons who have MS and have been associated with decreased adherence to MS treatment and poorer functional status and quality of life. Effective treatment is available for MDD, but this disorder continues to be underdetected and undertreated by MS providers. Treatment with pharmacotherapy is particularly challenging in this patient population, given the somatic symptom overlap between MS and depression and the increased burden of side effects. Larger randomized, controlled trials are needed to elucidate further the effectiveness of pharmacotherapy and to identify subgroups of patients who would benefit from this type of treatment for depression. There have been few rigorous studies of the prevalence and impact of anxiety disorders, substance use disorders, or serious mental illness such as bipolar disorder or schizophrenia, in MS samples.     

Gender issues and multiple sclerosis

Gender-related issues in multiple sclerosis include the important and widely accepted clinical observations that men are less susceptible to the disease than women and also that disease activity in multiple sclerosis is decreased during late pregnancy. This article reviews mechanisms underlying each of these clinical observations and discusses the role of sex hormones in each. Specifically, the protective role of testosterone in young men and the protective role of the pregnancy hormone estriol in pregnant women are discussed. Rationale for novel therapies in multiple sclerosis based on the protective roles of these sex hormones is presented.     

Selected issues of immunomodulating treatment in multiple sclerosis

Placebo-controlled or open trials of immunomodulating drugs shed more light upon pivotal clinical issues in relapsing-remitting and secondary progressive multiple sclerosis (RR MS, SP MS). Extension over 4 years of IFN beta-1b, IFN beta-1a s.c. and glatiramer acetate trials provided modest clinical benefit in RR MS patients. After 4-8 years of treatment an annual relapse rate decreased (0.20-0.57) and proportion of progression free RR MS patients increased significantly (56-65%). The percentages of SP MS patients without relapses increased markedly in EUSPMS, IMPACT, NASMPS and SPECTRIMS trials to 36-63. However, the treatments did not slow progression in two latter clinical investigations (p=ns). In most non-responders to IFN beta the second-line immunomodulating drugs brought about clinical improvement. About half of MS patients showed one year or longer adherence to the first immunomodulating drug and nearly one fifth benefited from the change of this drug to another immunotherapeutic agent.     

Clinical trials in multiple sclerosis: methodological issues

PURPOSE OF REVIEW: The availability of partially effective immunomodulatory and immunosuppressive treatments for relapsing multiple sclerosis (MS) opens important ethical, methodological and practical issues in the design and conduct of new clinical trials in these patients. RECENT FINDINGS: The recommendation of the National Health Authorities to prioritize phase III clinical trials using placebo arm raises ethical questions. In addition, patients are reluctant to be involved in such trials. Alternative clinical trial designs will be discussed. Relapses and active lesions are accepted measures of disease activity; new/enlarging T2 lesions and/or enhancing lesions are accepted surrogate markers of disease activity in phase II clinical trials. On the contrary, there are no accepted magnetic resonance imaging (MRI) surrogate markers of disease progression and also the clinical measures to monitor the degenerative aspects of the disease are not without important limitations. New scales of impairment, disability and quality of life will be reviewed extensively. We will also focus on the value of modern and quantitative MRI techniques, which hold substantial promise as tools to estimate the extent of MS-related irreversible tissue loss. SUMMARY: The use of an active comparator in a superior clinical-trial design is becoming an attractive option for testing the efficacy of new drugs in relapsing MS. At present there are no fully reliable and sensitive clinical markers of the accumulation of irreversible tissue damage in MS. Although additional extensive application in longitudinal studies is needed, modern MRI techniques are promising tools to monitor the neurodegenerative aspects of MS.     

Ethical issues in multiple sclerosis under physicians and patients point of view

Multiple sclerosis (MS) is a neurologic disorder that mostly affects young adults and can usually evolute to physical disability. Thus, caring patients with MS brings many ethic questions for the physician. OBJECTIVE: To identify physicians and patients' perceptions about the illness and so improve doctor-patient relationship. METHOD: It was made two different questionnaires, one for patients and another for physicians, 103 patients and 44 physicians answered them. RESULTS: 96.1% of patients knew their diagnosis, all others would like to know it. From those, 74.7% thought that that way it was disclosured was correct and 90.9% said that the doctor should tell us it. The worst symptoms described were fatigue (29.1%) and motor deficits (28.1%). By other side, 68% of patients told they suffered because of the illness. The most important reason for doctors to tell the diagnosis to the patients was to improve adherence to treatment (56.8%). A familiar present at this moment was demanded for 54.6% of doctors. When asked about orientations in a pregnancy, 50% of physicians did not answer correctly. Finally, 50% of physicians were against complementary and alternative therapies. CONCLUSION: Patients want to know their diagnosis and doctors should tell them in the most adequate moment and give more information. A debate about palliative care is also necessary.     

Higher than expected prevalence of multiple sclerosis in northern Colorado: dependence on methodologic issues

A population-based study of multiple sclerosis (MS) was conducted in 2 northern Colorado counties in 1982 to determine MS prevalence, to compare the rates with recent North American surveys and to compare the methods used in these studies. Provisional cases were identified from: the patient rolls of MS service organizations, chart reviews in 2 neurology practices, a survey of physicians and a review of hospital discharge diagnoses. Crude-point prevalence for the 2-county region was 84 per 100,000. The age-adjusted rate was higher than the rate for the region above the 37th parallel projected from data in a 1976 national survey, but was comparable to rates obtained in localized surveys conducted in the northern tier of the country. The methodological results revealed that the highest yield sources were the MS service organizations and the neurology practice chart reviews. MS prevalence surveys which neglect these methods may underestimate MS prevalence by as much as 20-40%.     

Management of pregnancy-related issues in multiple sclerosis patients: the need for an interdisciplinary approach

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS), most probably autoimmune in origin, usually occurring in young adults with a female/male prevalence of approximately 3:1. Women with MS in the reproductive age may face challenging issues in reconciling the desire for parenthood with their condition, owing to the possible influence both on the ongoing or planned treatment with the possible consequences on the disease course and on the potential negative effects of treatments on foetal and pregnancy outcomes. At MS diagnosis, timely counselling should promote informed parenthood, while disease evolution should be assessed before making therapeutic decisions. Current guidelines advise the discontinuation of any treatment during pregnancy, with possible exceptions for some treatments in patients with very active disease. Relapses decline during pregnancy but are more frequent during puerperium, when MS therapy should be promptly resumed in most of the cases. First-line immunomodulatory agents, such as interferon-β (IFN-β) and glatiramer acetate (GA), significantly reduce the post-partum risk of relapse. Due to substantial evidence of safety with the use of GA during pregnancy, a recent change in European marketing authorization removed the pregnancy contraindication for GA. This paper reports a consensus of Italian experts involved in MS management, including neurologists, gynaecologists and psychologists. This consensus, based on a review of the available scientific evidence, promoted an interdisciplinary approach to the management of pregnancy in MS women.     

Paraesthesiae in multiple sclerosis

The clinical features of paraesthesiae were analysed in 127 patients with clinically definite multiple sclerosis (MS). Fifty-one of these patients (40%) mentioned paraesthesia as a presenting symptom and 107 (84%) had persistent paraesthesiae by the time of this study. Paraesthesiae were frequently associated with sensory loss in the same region. However, this association was not statistically significant nor was that between the occurrence of paraesthesiae and abnormal somatosensory evoked responses (SSER). Statistically significant associations were found between abnormal SSER and abnormal sense of vibration, abnormal SSER and diminished sense of touch, and abnormal SSER and diminished sense of pain.     

Fatigue in multiple sclerosis

Fatigue is a frequent symptom in multiple sclerosis (MS) that can interfere with a patient's daily functioning. The cause of MS fatigue, its clinical characteristics, and its relationship to other symptoms remain poorly understood. Structured interviews were conducted with 32 patients with MS and 33 normal healthy adults. Fatigue proved to be both more frequent and more severe among the patients with MS. Multiple sclerosis fatigue was unrelated to either depression or global impairment. Multiple sclerosis fatigue appears to be a distinct clinical entity, often disabling, that can be distinguished from normal fatigue, affective disturbance, and neurologic impairment.     

Neurophysiology in multiple sclerosis

Different types of conduction defects, avenues available for functional recovery after demyelination, therapeutic and diagnostic measures, and electrophysiologic testing are covered.     

Neurorehabilitation in multiple sclerosis

Neurorehabilitation is predominantly an educational, dynamic process based on the adaptation of the individual and his environment to the actual neurological impairment and focuses on decreasing the impact of disabling neurological conditions on the individual in order to achieve optimum quality of life. It has been suggested by some that neurorehabilitation is the only approach available to us which can improve the limitations in activity and restrictions in social participation of people with multiple sclerosis. The neurorehabilitation approach is a holistic one and is a fundamental part of neurological care; it should not be forgotten by neurologists, especially when dealing with people with chronic disabling conditions such as multiple sclerosis. Together with the social model of disability, the concept of restorative neurology, as a scientific and therapeutic attempt to minimize those impairments directly responsible for the disability presented by the person, is recently gaining ground among neuroscientists and clinicians. In this review the conceptual basis for neurorehabilitation will be presented together with a review of the literature concerning the biological aspects of neurorehabilitative therapy (neuroplasticity) and the clinical trials evaluating the effectiveness of neurorehabilitation in people with multiple sclerosis. Finally, we will consider the practical aspects of neurorehabilitation.     

Metamemory in multiple sclerosis

Abstract

MS patients and age- and education-matched normal controls were administered several laboratory tests of metamemory and a questionnaire designed to measure subjects' capability to appraise their ability to remember events that might occur in everyday life. On laboratory tasks involving newly acquired information, MS patients with poor recognition memory abilities or poor performance on the Wisconsin Card Sorting Test (WCST) exhibited impairments on one test of metamemory; patients with deficits in both recognition and on the WCST showed more extensive impairments in metamemory. In contrast to their performance on tests involving newly acquired information, all groups of MS patients predicted their ability to recognize answers to general information questions that they could not recall as accurately as controls, and, like controls, they also searched their memories longer for answers to items that they believed they would recognize. In general, the results support the hypothesis that both trace-access and inferential mechanisms, which are thought to involve the prefrontal cortex, contribute to metamemory, but the nature of the memory task importantly influences the accuracy of metamemory, as well. Results from the questionnaire indicated that many MS patients with demonstrable memory deficits do not acknowledge their memory difficulties. Hence, patient self-reports about memory are likely to be unreliable sources of information for clinical purposes.