Influence of prostaglandin E2 and indomethacin on interferon-gamma production by cultured peripheral blood leukocytes of multiple sclerosis patients and healthy donors

The addition of indomethacin to concanavalin A (Con A)-induced cultures of human peripheral blood leukocytes (PBL) caused an increase in interferon response, regardless of whether the PBLs were derived from multiple sclerosis (MS) patients or from control donors. Specifically the response rates increased from 71 to 100% in controls and from 24 to 53% in MS patient-derived cultures. The amounts of interferon produced also increased in both groups by 0.8 log U/ml. However, interferon yields of nonresponsive cultures becoming interferon-producing only after indomethacin treatment remained relatively low. In control cultures, maximal increases of interferon production were obtained with doses of 0.05 to 0.1 microgram/ml indomethacin; for MS patients higher doses were needed--0.1 to 0.5 microgram/ml. Conversely, a relatively low dose (0.05 microgram/ml) of exogenous prostaglandin E2 (PGE2) was able to inhibit interferon production completely in MS patient-derived cultures, whereas in control cultures higher doses were needed (0.1 to 1.0 microgram/ml). Analysis of endogenous PGE2 levels in the PBL cultures revealed that PGE2 production was similar in nonresponder MS cultures and responder control cultures but that MS leukocytes were more sensitive to the inhibitory effect of PGE2 on interferon production. We conclude that in a minor percentage of MS patient-derived PBL cultures, the deficiency in interferon-gamma (IFN-gamma) production can be (partially) overcome by treatment of the cells with indomethacin. However, in the major part of nonresponder MS cultures, indomethacin has no effect, indicating that the PG system is not the major cause for the defective interferon response in MS.status: publishe

A quantitative study of unpaid caregiving in multiple sclerosis

Data on healthcare utilisation by MS patients of different grades of disability were collected using the method of a prospective diary. Professional care providers and unpaid caregivers noted during 4 weeks the time they spent and the types of support they provided. The total homecaring time of family and friends amounted to 4.6 and 12 h per day for the moderately and the severely disabled MS patients respectively. The time for unpaid core activities such as mobility help, nursing care and personal care of moderately and severely disabled patients amounted to 0.5 and 2 h per day, exceeding the time for professional medical and paramedical care at home. Eighty per cent of informal homecaring is provided by persons living with the patients, primarily the partner, who provides 60% of homecaring time. Severely disturbed bowel function and absence of a partner were associated with permanent institutionalisation. Multiple Sclerosis (2000) 6 274 - 279status: publishe

Improvement of health-related quality of life in relapsing remitting multiple sclerosis patients after 2 years of treatment with intramuscular interferon-beta-1a

In patients with relapsing remitting multiple sclerosis (RRMS), the effect of interferon-beta (INFb) on health-related quality of life (HR-QoL) is not firmly documented. The objective of this study is to assess HR-QoL during 2 years of treatment with intramuscular INFb and its correlation with disability. In 36 neurological practices in the Netherlands (17), Belgium (16), United Kingdom (2) and Luxemburg (1), 284 RRMS patients were treated with intramuscular INFb-1a. Physical and mental domains of HR-QoL were measured by the MS54 Quality of Life (MS54QoL) questionnaire, and disability was assessed by the Multiple Sclerosis Functional Composite (MSFC) (Timed 25-Foot Walk Test [Timed 25-FWT], 9 Hole Peg Test [9-HPT], Paced Auditory Serial Addition Test [PASAT]) at baseline and at months 3, 6, 12, 18 and 24. Expanded Disability Status Scale (EDSS) score was assessed at baseline and month 24. Pearson's correlation coefficients were determined and predefined factors were analyzed for relation to HR-QoL after baseline by stepwise regression analyses on physical and mental scores. 204 patients (71.8%) completed 2 years of treatment. Mean values for MS54QoL increased from 56.6 to 61.0 for physical (p < 0.05) and from 57.2 to 61.1 for mental domain (p = 0.07). Correlations between physical domain and MSFC was -0.40 (p < 0.05), and between mental domain and MSFC -0.24 (p < 0.05). MSFC and EDSS did not change. Increase of physical MS54QoL was associated with lower age, lower EDSS, less time for Timed 25-FWT, and higher PASAT score at baseline. Increase of mental MS54QoL was associated with higher PASAT and lower EDSS. Patients who discontinued INFb had lower physical or mental HR-QoL at baseline. In RRMS patients, 2 years of treatment with intramuscular INFb-1a is associated with an increase in HR-QoL, especially in younger patients with low disability

Neuropathological examination of the alterations of the intrinsic innervation in multiple sclerosis cystopathy.

Morphometric analysis of the innervation pattern of the stromal layer of the urinary bladder was done on biopsies from 88 patients with definite multiple sclerosis (MS). The biopsies were stained for acetylcholinesterase and for S100 protein, and a semiquantitative score was assigned. Nearly 30% of the samples showed increased immunoreactivity for S100, indicating Schwann cell hyperplasia. In 16% a decreased S100 immunoreactivity was found, the significance of which is unclear. More than 90% had normal acetylcholinesterase activity. No correlation could be demonstrated for age, sex, severity and duration of the disease, the presence of cystitis and type of detrusor dysfunction. The finding of altered S100 immunoreactivity in MS bladders could indicate that MS also affects the peripheral nervous system and is not limited to the central nervous system as classically described. This finding warrants further investigations

The epidemiology of multiple sclerosis in Europe

Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences. It is the major cause of non-traumatic disability in young adults. The social costs associated with MS are high because of its long duration, the early loss of productivity, the need for assistance in activities of daily living and the use of immunomodulatory treatments and multidisciplinary health care. Available MS epidemiological estimates are aimed at providing a measure of the disease burden in Europe. The total estimated prevalence rate of MS for the past three decades is 83 per 100 000 with higher rates in northern countries and a female:male ratio around 2.0. Prevalence rates are higher for women for all countries considered. The highest prevalence rates have been estimated for the age group 35–64 years for both sexes and for all countries. The estimated European mean annual MS incidence rate is 4.3 cases per 100 000. The mean distribution by disease course and by disability is also reported. Despite the wealth of epidemiological data on MS, comparing epidemiological indices among European countries is a hard task and often leads only to approximate estimates. This represents a major methodological concern when evaluating the MS burden in Europe and when implementing specific cost-of-illness studies

A double-blind clinical trial of mitoxantrone versus methylprednisolone in relapsing, secondary progressive multiple sclerosis.

A double-blind clinical trial of mitoxantrone versus methylprednisolone was performed in 49 patients with relapsing, secondary multiple sclerosis. Patients were randomized to receive 13 infusions of mitoxantrone 12 mg/m2 (n = 28), or 13 infusions of 1 g of methylprednisolone (n = 21), over 32 months. Twenty-four patients completed the trial. There were no statistical differences between the two groups of patients at study entry. A significant improvement in the Expanded Disability Scale Score (EDSS) was observed in the mitoxantrone group after one year of treatment (p < 0.0022). The total number of relapses, the mean number of relapses/patient/year, and the total number of gadolinium-enhanced lesions on bi-annual MRI scans were significantly decreased in the mitoxantrone group throughout the study period. Nausea, vomiting, and alopecia were more frequent in the mitoxantrone-treated patients. Mitoxantrone has a role in the treatment of MS patients with frequent exacerbations and rapid disease progression

Neuropathology of two Brazilian autopsied cases of tropical spastic paraparesis / HTLV-I associated myelopathy (TSP/HAM) of long evolution.

We report on a neuropathological analysis of two cases of TSP/HAM originating from Brazil. These two cases had, respectively, an evolution of 13 and 40 years. The main neuropathological findings consisted of spinal cord atrophy, mainly the lower thoracic cord, diffuse degeneration of the white and grey matter, rare foci of mononuclear and perivascular cuffs, and hyaline hardening of arteriolae. The supraspinal structures were normal, excepting for a slight gliosis in the cerebellum. An analysis on the long evolutive cases as described in the literature is outlined in this study