Stress constitutes a risk factor for diseases where the immune system plays a significant role. Stress is recognized as a possible trigger for flare ups during the course of multiple sclerosis (MS). The disclosure to the patient of the diagnosis of MS, the commencement of immunomodulatory therapy, and the unpredictability and vagaries of disease progression are all sources of stress. Biological stress systems such as the hypothalamic-pituitary-adrenal system and the sympathetic nervous system may influence the pathogenesis and the disease course of MS. The ability to cope with stress may also be impaired, mediated for example by cognitive deficits or loss of abilities and resources as disease progresses or by the high prevalence of concurrent mood disturbances such as depression and chronic fatigue. Psychiatric comorbidities of MS disease or therapy as well as impairments of coping strategies are underrecognized in clinical practice. Treatment plans for depression among MS patients, as the most common psychiatric comorbidity, should be individualized with integrated approaches. Antidepressants are effective for the treatment of depression in MS patients although further clinical research into the neurobiological and psychological bases of depressive disorders in MS patients is clearly needed. In therapy, coping strategies can be enhanced through multidisciplinary assessment of the various challenges and restrictions imposed by the disease and assisting and supporting the patient in addressing these. Exercise, as a form of positive stress (eustress), also has a role in therapy.
In brain MRI of multiple sclerosis (MS) patients, enhancement of the lesions is usually evaluated in early contrast-enhanced T1-weighted images (CE-T1WI). The objective of this study is to determine the sensitivity of contrast-enhanced fluid-attenuated-inversion-recovery (CE-FLAIR) and delayed contrast-enhanced MRI in evaluation of MS brain lesions.
Brain MRI examination including early and delayed CE-T1WI and early and delayed CE-FLAIR images was performed for 46 patients with clinically definite MS disease. Number, size, location, degree, and pattern of enhancement of the enhanced lesions in each sequence were recorded separately.
A total number of 87 enhanced lesions was detected in 30 patients. Early CE-T1WI could detect only 63 lesions (72.4% of total) in 24 patients, while delayed CE-T1WI and early and delayed CE-FLAIR images showed 85 (97.7%), 84 (96.6%), and 81 (93.1%) lesions in 28, 28, and 26 patients, respectively. A greater degree of enhancement and larger lesion size were observed in the additional sequences compared with the early CE-T1WI.
The sensitivity of early CE-T1WI for the detection of enhanced MS lesions is significantly lower than that for other additional sequences. Delayed CE-FLAIR images could not add significant information to other sequences. Therefore, early CE-FLAIR and delayed CE-T1WI brain MRI can be considered as part of the evaluation of MS patients, especially if, despite clinically suspected active disease, no enhanced lesion is found in the routine CE-T1WI.
The onset of multiple sclerosis is being increasingly recognized in children and adolescents. There are now approved immunomodulatory therapies for adults with multiple sclerosis. Treatment early in the disease course appears to have a greater impact on disease outcome, an issue of particular importance for children who face decades of multiple sclerosis disease activity. This review summarizes the multiple sclerosis therapies currently available, efficacy data available from studies of these medications in adults and limited information on the use of these medications in children. Future directions in multiple sclerosis therapeutics and specific issues relating to pediatric multiple sclerosis are discussed.
The objective of this study is to determine the effect of oral ketamine on pain and allodynia associated with multiple sclerosis. A 60-year-old woman with multiple sclerosis was referred to our clinic because of severe pain and allodynia. Oral ketamine was started at a dose of 20 mg once a day and increased to twice a day. Oral ketamine was effective in the treatment of the pain and allodynia associated with multiple sclerosis.
During the past 2 decades, the considerable improvement of magnetic resonance (MR) technology and the development of new MR strategies capable of providing an in vivo overall assessment of multiple sclerosis (MS) pathology have allowed us to obtain important novel pieces of information on disease evolution in the brain. However, despite this, the correlation between brain MR imaging metrics and clinical disability are still suboptimal. A reason for this discrepancy might be the involvement of clinically eloquent structures, such as the spinal cord, which owing to technical challenges have not been extensively studied using MR imaging until very recently. An objective and accurate estimate of the presence and extent of spinal cord damage might indeed contribute to increasing the strength of the correlations between clinical and MRI metrics. This review summarizes the main results obtained from the application of conventional and modern MR-based techniques for the evaluation of spinal cord damage in MS.
The aim of this study is to evaluate the prevalence of the clinical and videofluoroscopic (VDF) symptoms of oropharyngeal dysphagia in patients with multiple sclerosis, and to describe its therapeutic management.
We studied 23 patients suffering from multiple sclerosis to evaluate the characteristics of the disease, the VDF exploration of swallowing and therapeutic strategies. The VDF exploration enables us to define the VDF symptoms that assess the safety and efficiency of swallowing for the oral and pharyngeal phases. The therapeutic strategies include: changes in the characteristics of the diet, changes of posture and active manoeuvres.
The patients studied presented a mean EDSS score 7.4 (4-9). There were alterations in swallowing efficiency and/or safety in more than 80% of the patients. In 52% there was some change in the swallowing safety. 40% of them were silent aspirators. All these patients were fed orally without any complications, in 78% the volume of the bolus has been modified and changes have taken place in the consistency (thickening for liquids); in 43%, moreover, postural strategies were employed and active manoeuvres (supraglottic swallow) were introduced in 13% in order to improve swallowing safety.
There is a high prevalence of clinical and VDF symptoms of oropharyngeal dysphagia in patients with advanced multiple sclerosis. VDF enables us to diagnose the pathophysiological mechanism of aspiration and the existence of silent aspirators, and helps us to introduce specific therapeutic interventions for each patient, thereby achieving safe and efficient swallowing, while prolonging oral feeding.
Antigen-coupled antigen-presenting cells (APC) serve as potent tolerogens for inhibiting immune responses in vivo and in vitro, apparently by providing an antigen-specific signal through the TCR in the absence of co-stimulation. Although this approach has been well studied in rodents, little is known about its effects on human T cells. We evaluated the specificity and mechanisms of tolerization of human T cells in vitro using monocyte-enriched adherent cells that were pulsed with antigen and treated with the cross-linker, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (ECDI). Autologous antigen-coupled APC selectively tolerized T cells of the T(h)1 but not T(h)2 lineage through a mechanism that involved both antigen-specific and antigen-non-specific elements. The tolerization process was dependent on the ECDI and antigen concentration, and the coupling time, and was reflected by initial up-regulation of CD25. However, upon re-stimulation with fresh APC and antigen, tolerized T(h)1 cells failed to proliferate or to produce T(h)1 cytokine message or secreted protein, had decreased expression of CD25, CD28 and B7 and increased expression of MHC class II molecules, and demonstrated an enhanced commitment to apoptosis. T(h)1 cell tolerization could be prevented by adding anti-CD28 antibody, IL-2 or untreated APC at the same time as the ECDI/antigen-coupled APC, or reversed by adding anti-CD28 antibody or IL-2 upon re-stimulation with fresh APC plus antigen. Thus, the tolerizing effect of ECDI/antigen-coupled APC on human T(h)1 cells appears to involve a reversible anergy mechanism leading to apoptosis, whereby the targeted T cells receive full or partial activation through the TCR, without coordinate co-stimulation. These data suggest dichotomous signaling requirements for inactivating cells of the T(h)1 and T(h)2 lineages that may have important implications for treatment of T(h)1-mediated autoimmune or inflammatory diseases.
In a 2-year hospital-based study in Jordan 131 Arab multiple sclerosis patients were identified including 84 Palestinians and 36 Jordanians. Based on MS/ALS case ratio, multiple sclerosis was found to be twice as common among Palestinians than Jordanians. Other than the less marked female preponderance among Jordanian patients, the disease had the same clinical and paraclinical characteristics in both groups. It was more likely for Palestinian and Jordanian patients to originate from the northern parts of their countries, to be Rh negative and to be HLA-DR2 positive than their controls. Palestinians (patients and controls) did not show significant differences from Jordanians (patients and controls) in relation to their eye color, ABO and Rh blood groups distribution nor the HLA-DR or HLA-DQ (apart from HLA-DQ3) epitopes frequency, thus not offering any significant difference in the genetic-racial markers studies to explain the difference in the observed disease susceptibility. Previous studies demonstrated that 2 racially different populations sharing the same environment can have different risk of developing multiple sclerosis, but this study has shown that this can also be true for 2 racially similar populations sharing the same environment.
Health care professionals participating in rehabilitation for people with MS can play a critical role in enhancing limited outcomes such as enhanced mobility, reductions in symptoms such as pain and depression, and the metaoutcome-participation. This role will be significantly more effective if the health care professional acknowledges and validates the different perspectives of the professional and the patient and recognizes the expertise of the patient who has lived with MS in the context of his or her life. Assuming this role effectively requires that the health care professional develop a collaborative relationship with the patient and understand that the role may change depending on the stage of MS and the individual's circumstances.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system of unknown etiology. Several viruses have been suggested as playing a role in the pathogenesis of MS. The aim of this study was to investigate the interrelationship of human herpesvirus 6 (HHV-6) and plasminogen activation at the cellular level in MS plaques.
Brain tissue specimens obtained from autopsies of 15 patients with MS and 10 controls were studied immunohistochemically for HHV-6 and cytomegalovirus (CMV) antigen and tissue plasminogen activator (tPA) protein. The presence of Ebstein-Barr virus (EBV) EBER RNA was studied using RNA in situ hybridization.
HHV-6 antigen was identified in the cells of 67% (10/15) of MS brain sections and 30% (3/10) of the control sections. All samples were negative for CMV antigen and all samples with intact RNA were negative for EBV EBER RNA as demonstrated by in situ hybridization. tPA expression was found to be increased in MS plaques compared with the control samples. Interestingly, in 5 MS samples both HHV-6 antigen and tPA stained clearly, compared with none in the controls, but HHV-6 and tPA only occasionally co-localized in the same cells.
At the cellular level, HHV-6 and plasminogen activation seem to co-localize in MS.