Swine influenza vaccination in patients with multiple sclerosis.

Swine influenza vaccination was tolerated well by 61 multiple sclerosis patients. A new neurologic symptom developed in one patient, one noticed the recurrence of previous symptoms, and two patients experienced systemic signs of toxicity.

The modification of experimental allergic encephalomyelitis with epsilon aminocaproic acid.

Epsilon aminocaproic acid, an inhibitor of plasminogen and trypsinogen activators, can decrease the severity of experimental allergic encephalomyelitis (EAE) in rats. The drug was tried because of a number of observations suggesting that neutral proteases, such as plasmin, might be chemical mediators of demyelination. The highest concentrations of plasminogen activator are found in the walls of veins and venules, around which demyelination is common in many demyelinating diseases, including MS. Indeed, the earliest lesion in MS is often demyelination with little cellular infiltration. In vitro studies have shown that neutral proteases secreted by activated macrophages selectively lyse myelin basic protein.

Seasonal variation of multiple sclerosis exacerbations in Arizona.

We studied 178 MS patients and 82 controls for 5 years. A monthly pattern in in the frequency of exacerbations in Arizona differed from the patterns seen in other regions of the world. Exacerbations were most common in warmer months. No explanation for this was found. In this prospective study, the frequency of viral infections in the MS patients was lower than in the controls.

Anamnestic studies in multiple sclerosis: a relationship between familial multiple sclerosis and neoplasia.

A survey of family histories of malignant neoplasia in multiple sclerosis (MS) patients indicates that a positive history of cancer in near relatives is present in 44 percent of patients and 46 percent of controls. However, those MS patients having such a positive history were much more likely than others to also have a family history of MS. Contrariwise, MS patients with a positive family history of MS had a significantly higher rate of cancer in first degree relatives (71 percent) than others. There was a trend indicating less cancer in families of MS patients possessing the HLA-B7 and DW2 histocompatibility antigens.

Trauma as an etiologic and aggravating factor in multiple sclerosis.

We carried out a retrospective and prospective epidemiologic study designed to detect an association between trauma and multiple sclerosis in 130 patients and 82 age- and sex-matched controls. Electrical injury was followed by an increased frequency of exacerbation, which did not achieve statistical significance. There was no statistically significant association between other types of trauma and onset or deterioration of the disease. These findings do not prove that such an association cannot exist for any one individual patient; however, they do not provide evidence to support this idea.

Corticosteroids or ACTH for acute exacerbations in multiple sclerosis.

BACKGROUND: Corticosteroids are often used to improve the rate of recovery from acute exacerbation in multiple sclerosis (MS) patients. However, it is still unclear just how relatively effective these agents are and the type of drug, optimal dose, frequency, duration of treatment and route of administration are unknown. OBJECTIVES: The object of this review was to determine the efficacy and safety of corticosteroids or ACTH in reducing the short and long term morbidity from MS. Moreover, we wished to examine from indirect comparisons if the effect of corticosteroids is different according to different doses and drugs, routes of administration, length of treatment. SEARCH STRATEGY: A search strategy developed for the Cochrane MS Group (last searched: June 1999) completed with handsearching and personal contacts with trialists and pharmaceutical companies was used. SELECTION CRITERIA: All randomised, double-blind, unconfounded trials comparing corticosteroids or ACTH to placebo in patients with MS, treated for acute exacerbations, without any age or severity restrictions, were evaluated. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected articles for inclusion, assessed trials' quality and extracted the data. A third reviewer cross-checked them and disagreements were resolved by a joint discussion. MAIN RESULTS: Six trials contributed to this review; a total of 377 participants (199 treatment, 178 placebo) were randomised. The drugs analysed were methylprednisolone (MP) (four trials, 140 patients) and ACTH (two trials, 237 patients). Overall, MP or ACTH showed a protective effect against the disease getting worse or stable within the first five weeks of treatment (odds ratio[OR]=0.37, 95% confidence interval [CI] 0.24-0.57) with some but non significant greater effect for MP and intravenous administration. Short (five days) or long (15 days) duration of treatment with MP did not show any significant difference. Only one study (with 51 patients) reported data after one year of follow-up: no difference between oral MP and placebo in the prevention of new exacerbations or improvement in long term disability was detected. No data are available beyond one year of follow-up to indicate whether steroids or ACTH have any effect on long-term progression. One study reported that a short term treatment with high dose intravenous MP was not attended by adverse events. On the contrary, gastrointestinal symptoms and psychic disorders were significantly more common in the oral, high-dose MP than in the placebo group. Weight gain and edema were significantly more frequent in the ACTH group than in controls. REVIEWER'S CONCLUSIONS: We found evidence favouring the corticosteroid MP for acute exacerbation in MS patients. Data are insufficient to reliably estimate effect of corticosteroids on prevention of new exacerbations and reduction of long-term disability. Studies assessing long term risk/benefit and adverse effects of corticosteroids in MS patients are urgently needed.

Spotlight series: pivotal trials through today's knowledge--adrenocorticotrophic hormone.

Forty-five years ago the first large multicentre, randomized, double-blinded, controlled trial of a potential therapy for multiple sclerosis (MS) was completed testing corticotrophin versus placebo. It demonstrated the feasibility of such a trial in an illness which is as variable, from patient to patient, as MS. Adrenocorticotrophic hormone was soon replaced by intravenous methylprednisolone (IVMP) as therapy for acute exacerbations, to control acute inflammatory responses. Long-term therapy with corticosteroids is fraught with complications. Pulsed IVMP has been widely used as an alternative, but few formal studies have been done. One, however, suggested that treated patients had less brain atrophy, and further study of this technique may be indicated.

Natural history and treatment of multiple sclerosis.

The course of multiple sclerosis (MS) evolves over decades. Recent advances in our understanding of the spectrum and variability of the course of MS over the long term in large geographically based populations, and over the short term in selected subgroups randomized to the placebo limbs of controlled clinical trials are discussed. Trials of several toxic immunosuppressive drugs and plasma exchange (PE) show that these methods of treatment are unlikely to help MS patients, although azathioprine has some rationale in rapidly advancing cases. The triggering of attacks by viral infections makes one await the results of current trials of interferon-beta with special interest.

Intranuclear inclusions in a case of Creutzfeldt-Jakob disease: an ultrastructural study.

Two types of intranuclear inclusions were described in a brain biopsy from a patient with Creutzfeldt-Jakob disease. The first type of intranculear inclusion was papova virus-like and was observed within 20% of the nuclei of all astrocytes and neurons examined. The particles measured 32 nm in diameter and consisted of a dense core surrounded by a multi-layered shell. The second type of intranuclear inculsion was a granulo-fibrillar nuclear body found within the nuclei of astrocytes and neurons. The possible significance of these inculsions to the etiology of Creutzfeldt-Jakob disease is discussed.

Clinical viral infections and multiple sclerosis.

Over an 8 year period, 170 patients with multiple sclerosis (MS) and 134 healthy controls were assessed at monthly intervals in order to ascertain environmental factors which might be important in producing exacerbation or progression of the illness, and to compare the frequency of common viral infections in the two groups. During cumulative periods designated "at risk" (2 weeks before the onset of infection until 5 weeks afterwards) annual exacerbation rates were almost 3-fold greater than those during periods not at risk. Approximately 9% of infections were temporally related to exacerbations, whereas 27% of exacerbations were related to infections. Frequency of common infections was approximately 20-50% less in MS patients than controls; it was progressively less in those with greater disability. Even in minimally disabled patients with similar potential for infectious contacts, the infection rate was significantly less than in controls, suggesting that MS patients could have superior immune defences against common viruses.