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PubMed2004

Primary progressive multiple sclerosis: cerebrospinal fluid considerations.

Diagnosing the 'primary progressive' form of multiple sclerosis (PPMS) requires assurance that other conditions that might cause a chronic inflammatory neurodegenerative central nervous system (CNS) disease have been ruled out. Both imaging and pathological studies have shown that this form of MS tends to be less inflammatory compared with either the relapsing-remitting or secondary progressive types. There are therefore many conditions that cause a slowly progressive wasting of the CNS that might be confused with MS. The new MS diagnostic scheme has made the presence of 'typical' MS abnormalities in the cerebrospinal fluid (CSF) a mandatory first criterion, but there may well be individuals that still have PPMS even in the absence of a typical MS CSF. Here we explore what the CSF can tell about an individual's disease process and outline the current state of the art in terms of CSF analysis. Used properly, the CSF can be very helpful in clarifying a diagnosis of PPMS.

Cerebrospinal Fluid↗
PubMed1982

Multiple sclerosis: trial of a synthetic polypeptide.

A synthetic polypeptide, copolymer I (COP I), composed of alanine, glutamic acid, lysine, and tyrosine, has been demonstrated to be nonencephalitogenic and nontoxic in laboratory animals, yet it is capable of suppressing experimental allergic encephalomyelitis. A preliminary open trial examined the ability of COP I to alter the course of disease in 12 patients with chronic progressive and 4 with exacerbating-remitting multiple sclerosis (MS). After therapy for as long as two years or more, no undesirable side reaction was noted in any patient. Three patients with chronic progressive MS and 2 with exacerbating-remitting disease are better. These results, which may represent simply a placebo effect or may be a significant response, are now being examined in randomized, placebo-controlled, double-blind pilot trials.

Adult↗
PubMed1996

Human T lymphotropic virus type I (HTLV-I)-specific T helper cell responses from HTLV-I seronegative patients with chronic myelopathy and MS in Japan.

Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to Adult T cell leukemia (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although most HAM/TSP patients have high anti-HTLV-I antibody titers in their sera, HTLV-I infected but seronegative patients with neurological diseases have been reported. To clarify whether seronegative, HTLV-I related neurological disease may exist, we have developed a method that measures the production of interleukin-2 (IL-2) from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I infected persons. This method is sensitive enough to detect exposure to HTLV-I before seroconversion or even before detection by PCR. We examined 12 patients with chronic progressive myelopathy and eight patients with multiple sclerosis (MS) in central Japan, where the prevalence rate of HTLV-I is between one and four percent among asymptomatic blood donors, using the IL-2 production assay. None of them were positive by the assay, suggesting seronegative HTLV-I myelopathy is very rare among patients with chronic progressive myelopathy and MS in Japan.

Adult↗
PubMedDate not supplied

Chronic sorrow in multiple sclerosis. A case study.

Multiple sclerosis, one of the most common chronic disabilities among young adults, may potentiate the occurrence of chronic sorrow. Chronic sorrow differs from acute grief because it is permanent, periodic, and progressive in nature; it may be a normal component of chronic illness and disability. This study describes one woman's experience with multiple sclerosis, her chronic sorrow about the trajectory of her disability, her progressive loss of bodily function, and the stigma of chronic illness. It also reports some of the feelings experienced by her husband, the primary caregiver.

Caregivers↗
PubMed1998

Assessment of memory in multiple sclerosis patients using the Memory Assessment Scale.

Previous assessment of memory function in multiple sclerosis patients has yielded mixed findings regarding the type and severity of memory deficits, which may be due to (1) differential selection of scales for memory assessment; (2) limited, inconsistent or weak reliability and validity data for the memory scales employed; (3) poor standardization techniques; (4) lack of theoretical foundation for the measure; and (5) limited control of confounding variables, e.g., education, age and the use of nonverbal memory tests. The purpose of the present study was to assess memory function in multiple sclerosis subjects using the verbal subtests of the Memory Assessment Scale, a relatively new measure designed to overcome many of the aforementioned problems. Participants included 57 patients diagnosed as relapsing-remitting, 47 diagnosed as chronic progressive (two generally recognized types of multiple sclerosis), and 132 control participants. A multivariate analysis controlling for age and verbal IQ was significant (Wilks = 5.64, p < .001). One way follow-up tests showed both groups with multiple sclerosis had significantly diminished performance across all memory variables when compared with controls, with the exception of List Clustering Acquisition. This indicated that the patients used clustering (mentally grouping similar words together) as often as controls did. These findings provide support for the presence of significant and consistent verbal memory impairment in multiple sclerosis patients and the particular importance of using psychometrically sound measures in the assessment of this population.

Adolescent↗
PubMedDate not supplied

Alternative methods of treatment used by multiple sclerosis patients in Poland.

BACKGROUND AND PURPOSE: Despite the great progress that has been made in medicine, treatment of many chronic diseases, including multiple sclerosis (MS), remains hardly effective. It has been reported that more and more MS patients worldwide are using alternative methods (AM). The aim of the present study is to evaluate this phenomenon in the Polish MS population. MATERIALS AND METHODS: To obtain more data about use of AM in Poland we distributed questionnaires among 210 MS patients treated in 3 hospitals in different regions of our country: Warsaw, Gdansk and Pila. RESULTS: 210 patients (136 females and 74 males) took part in the study. 68.5% (144 of 210 questioned) declared use of AM now or in the past. The most popular (56%) was Oenothera seed oil, followed by vitamins (49%), and the third most common was massage (34%). There were no significant demographic differences between users and non-users. Neither disease duration nor disability had any impact on the decision to use AM. CONCLUSIONS: The phenomenon of use of AM by MS patients is not fully understood, but it seems that limited access to so-called immunomodulators, e.g. interferon-b or glatiramer acetate, and limited long-term efficacy are reasons why patients seek other therapies.

Complementary Therapies↗
PubMed1993

The germline repertoire of T cell receptor beta-chain genes in multiple sclerosis patients from Spain.

Recently several reports have described contradictory results after studying the association between restriction fragments length polymorphisms (RFLP) of T cell receptor (TcR) beta-chain genes and multiple sclerosis (MS). We studied the allelic, genotypic and haplotypic distribution of RFLPs of TcR beta chain gene segments C beta, V beta 8 and V beta 11 in 97 unrelated multiple sclerosis (MS) patients, 11 with chronic progressive MS and 86 with relapsing/remitting (R/R) MS. We found the distribution of the TcR haplotypes defined by the alleles of the three loci studied in the MS patients was significantly different from that found in control individuals. The distribution of TcR haplotypes in R/R MS patients was also different from that observed in controls. Our data suggest that the TcR beta chain gene complex contains one or more genes involved in genetic susceptibility to develop MS.

Alleles↗
PubMed1988

Interleukin-1 and interleukin-2 production by peripheral blood mononuclear cells in multiple sclerosis patients.

The production of interleukin-1 (IL-1) and interleukin-2 (IL-2) by peripheral blood mononuclear cells (PBM) was assessed in multiple sclerosis (MS) patients in relapse, chronic progressive MS patients, patients with other neurological diseases (OND) and healthy subjects. Production was defined as the level of IL-1 and IL-2 in PBM supernatants. Neither spontaneous nor LPS-induced IL-1 production differed significantly in MS, OND patients or healthy individuals. On the other hand PHA-induced PBM IL-2 production was significantly less in MS patients in relapse (130 +/- 10.0 U/ml) than in chronic progressive MS patients (172 +/- 9.8 U/ml), OND patients (192 +/- 11.5 U/ml) and healthy subjects (215 +/- 13.8 U/ml) (P less than 0.02). Spontaneous IL-2 production was also diminished in MS patients in relapse (31 +/- 7.2 U/ml) as compared to chronic progressive MS patients (46 +/- 8.8 U/ml) and healthy subjects (49 +/- 11.1 U/ml) (P less than 0.01). Anti-Tac monoclonal antibody was used to study IL-2 receptor expression on the same sample of PBM that was used for IL-2 study. MS patients in relapse had significantly higher levels of IL-2 receptor-positive unstimulated PBM (6.0 +/- 2.2%) as compared to chronic progressive MS (2.0 +/- 0.9%), OND (2.5 +/- 1.1%) and healthy subjects (1.5 +/- 0.7%) (P less than 0.002). We postulate that reduced apparent IL-2 production by PBM of MS patients in relapse may result from immediate IL-2 binding to receptor expressed on activated T lymphocytes and internalization of IL-2-receptor complex.

Adult↗
PubMedDate not supplied

Reduction of circulating suppressor inducer T lymphocytes in the exacerbation phase of remitting-relapse multiple sclerosis.

We studied peripheral blood mononuclear cells (PBMC) from 34 multiple sclerosis (MS) patients: 8 had chronic progressive (CP) and 26 with a relapsing-remitting (RR) course. PBMC were tested with a panel of monoclonal antibodies (MoAbs) including anti-CD3, CD4, CD8, CD25 reagents. In addition, the suppressor inducer lymphocyte subset was investigated by using two color staining with anti-CD4 and G1-15 and/or anti-CD4 and anti-Leu-8 MoaAbs. A significant decrease of the suppressor inducer subset was found in the exacerbation phase of the RR form. Furthermore, a significant decrease of CD8+ (suppressor/cytotoxic) cells was shown in the remission phase of the RR group. Finally, CD25+ lymphocytes were significantly increased in both phases of RR form.

Adult↗
PubMedDate not supplied

The diagnosis of multiple sclerosis: Peplau's Interpersonal Relations Model in practice.

Multiple sclerosis (MS) is a chronic, frequently progressive neurological disease of unknown etiology and uncertain trajectory. Physicians and nurses have historically been uncomfortable broaching the topic of a possible MS diagnosis with patients and have tended instead to talk about it in euphemistic terms. However, with the development of therapeutic agents that may be more effective early in the disease course, the early communication of diagnostic and treatment information has become increasingly important. In our MS clinic, individual with MS symptoms are rapidly referred and assessed by a team of experienced physicians and nurses. Our experience with this referral process has led to our adoption of Peplau's Interpersonal Relations Model as a guide to nursing practice. The central element of Peplau's model is the development of a therapeutic relationship between patient and nurse. This relationship develops through four overlapping stages: orientation, identification, exploitation, and resolution. The collaborative relationship that develops between nurse and patient enhances problem solving and creates a strong bond that is essential across the long trajectory of the illness.

Adaptation, Psychological↗
PubMed2001

Unit management of depression of patients with multiple sclerosis using cognitive remediation strategies: a preliminary study.

Multiple sclerosis (MS) is a chronic, often progressive neurologic disorder characterized by cerebral and spinal cord lesions. Patients with advanced MS often require continuous supervision in a long-term skilled nursing facility. Many of these patients experience clinical levels of depression. For this experiment, we randomly assigned MS patients living in a skilled nursing facility to either a control condition or an extended treatment protocol. The protocol consisted of assigning individual certified nursing assistants (CNAs) to each patient, in-service training for the CNAs, and the use of memory notebooks. All patients completed the short version of the Beck Depression Inventory and several measures of cognitive functioning at the start and end of the study. The results indicate statistically and clinically significant improvements in the depression of patients in the treatment but not in the control condition. These results led to recommendations for the treatment of MS patients living in long-term skilled nursing facilities and for additional research.

Cognition Disorders↗
PubMed1994

Serial contrast-enhanced magnetic resonance imaging in patients with early relapsing-remitting multiple sclerosis: implications for treatment trials.

Serial monthly contrast-enhanced MRIs were performed in 10 early relapsing-remitting patients with multiple sclerosis and 2 patients with chronic progressive disease for a period of 12 to 55 months. MRI was performed at 1.5 T using contiguous 5-mm slices with pre- and postgadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) T1-weighted and T2-weighted images. New and total number of Gd-DTPA-enhancing lesions were numbered and counted and lesion areas were correlated to an increase of > or = 0.5 in Expanded Disability Status Scale (EDSS) scores. The frequency of enhancing lesions varied from patient to patient; however, there was a correlation between a burst of enhancing lesion number and area above the individual's mean lesion frequency to an increase in EDSS score. A bootstrap analysis of the lesion count was performed to develop a statistical basis for determining population sizes for treatment trials. These results provide a basis for the potential use of contrast-enhanced MRI as a primary outcome measure in phase II treatment trials involving patients with relapsing-remitting MS.

Adult↗
PubMed1997

Progressive cognitive improvement in multiple sclerosis from treatment with electromagnetic fields.

It has long been recognized that cognitive impairment occurs in patients with multiple sclerosis (MS) particularly among patients with a chronic progressive course. MS is considered a type of "subcortical dementia" in which cognitive and behavioral abnormalities resemble those observed in patients with a frontal lobe syndrome. The Bicycle Drawing Test is employed for the neuropsychological assessment of cognitive impairment specifically that of mechanical reasoning and visuographic functioning. It also provides clues concerning the patient's organizational skills which are subserved by the frontal lobes. Extracerebral pulsed applications of picotesla flux intensity electromagnetic fields (EMFs) have been shown to improve cognitive functions in patients with MS. I present three patients with long standing symptoms of MS who, on the initial baseline, pretreatment Bicycle Drawing Test, exhibited cognitive impairment manifested by omissions of essential details and deficient organizational skills. All patients demonstrated progressive improvement in their performance during treatment with EMFs lasting from 6-18 months. The improvement in cognitive functions, which occurred during the initial phases of the treatment, was striking for the changes in organizational skills reflecting frontal lobe functions. These findings demonstrate that progressive recovery of cognitive functions in MS patients are observed over time through continued administration of picotesla flux intensity EMFs. It is believed that the beneficial cognitive effects of these EMFs are related to increased synaptic neurotransmission and that the progressive cognitive improvement noted in these patients is associated with slow recovery of synaptic functions in monoaminergic neurons of the frontal lobe or its projections from subcortical areas.

Adult↗
PubMed2003

Impaired remyelination and depletion of oligodendrocyte progenitors does not occur following repeated episodes of focal demyelination in the rat central nervous system.

It has been hypothesized that the progressive failure of remyelination in chronic multiple sclerosis is, in part, the consequence of repeated episodes of demyelination at the same site, eventually depleting oligodendrocyte progenitor cells (OPCs) and exhausting the remyelinating capacity. We investigated the effect of previous focal, ethidium bromide-induced demyelination of brain stem white matter (with intervening recovery) on the efficiency of the remyelination process during second and third subsequent episodes of demyelination, and the OPC response during a second episode of demyelination. Previous focal demyelinating lesions followed by recovery did not result in any retardation of the remyelination process, nor did they alter the proportion of Schwann cell versus oligodendrocyte remyelination. The OPC response during remyelination was quantified by in situ hybridization using a probe to platelet-derived growth factor-alpha receptor (PDGF alpha R), an OPC-expressed mRNA. Following recovery from focal, toxin-induced CNS demyelination, the OPC density returned to levels equivalent to those in normal white matter. Further more, there was no depletion of OPCs following repeated episodes of focal, toxin-induced CNS demyelination at the same site. These results indicate that repeated CNS demyelination, which has the opportunity to repair in the intervening period, is not characterized by impaired remyelination or depletion of OPCs.

Animals↗
PubMed2002

The palmitoylethanolamide family: a new class of anti-inflammatory agents?

The discovery of anandamide as an endogenous ligand for the cannabinoid receptors has led to a resurgence of interest in the fatty acid amides. However, N-palmitoylethanolamine (PEA), a shorter and fully saturated analogue of anandamide, has been known since the fifties. This endogenous compound is a member of the N-acylethanolamines, found in most mammalian tissues. PEA is accumulated during inflammation and has been demonstrated to have a number of anti-inflammatory effects, including beneficial effects in clinically relevant animal models of inflammatory pain. It is now engaged in phase II clinical development, and two studies regarding the treatment of chronic lumbosciatalgia and multiple sclerosis are in progress. However, its precise mechanism of action remains debated. In the present review, the biochemical and pharmacological properties of PEA are discussed, in particular with respect to its analgesic and anti-inflammatory properties.

Amides↗
PubMed1990

[HTLV-I retrovirus in Chile: study on 140 neurological patients].

We screened 140 patients with different neurological diseases for the presence of anti HTLV-1 virus antibodies. ELISA test confirmed with Western Blot analysis was performed in CSF and blood. Positive findings were obtained in 23 out of 52 patients with progressive spastic paraparesis (44%). All patients with multiple sclerosis, polymyositis, amyotrophic lateral sclerosis or chronic polyneuropathy were negative. Patients with progressive spastic paraparesis and positive HTLV-1 antibodies were most commonly women (78%) and middle aged (mean 46 years old), with a history of surgical interventions (70%) or blood transfusion (35%). A slowly progressive spastic paraparesis with asymmetric onset and minimal sensory complaints was observed in some cases. Mononuclear pleocytosis in the CSF was observed in 35% with an increased IgG index in 88%. A delayed latency and low amplitude of somatosensory evoked potentials was observed in 89% of patients.

Adolescent↗
PubMed1988

Determination of activated lymphocytes in peripheral blood of patients with multiple sclerosis.

Using monoclonal antibodies Ta1 and CD25 (interleukin-2 receptor: I-2R) and flow cytometry, the levels of activated lymphocytes in the peripheral blood of 50 patients with multiple sclerosis (16 relapsing inactive; 14 relapsing active; 20 chronic progressive) and 20 normal subjects were investigated. No significant differences were observed in the percentage or absolute numbers of Ta1 and IL-2R reactive lymphocytes between the normal and multiple sclerosis patient groups, irrespective of disease activity. Monitoring peripheral blood lymphocytes with respect to these markers would appear to have little value in the management of multiple sclerosis.

Humans↗