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.

Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis.

The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."

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.

Cerebral infarction immediately after ingestion of hydrogen peroxide solution.

BACKGROUND: We report the clinical and neuroimaging findings of a patient who sustained multiple cerebral infarcts after the ingestion of concentrated hydrogen peroxide solution sold as a "health food" product. CASE DESCRIPTION: An 84-year-old man sustained focal neurological deficits immediately after ingesting 30 mL of 35% hydrogen peroxide solution. Physical examination disclosed a left hemiparesis, frontal release signs, and cerebellar dysfunctions. Magnetic resonance imaging revealed multiple cerebral and cerebellar infarctions in the anterior, middle, and posterior vascular territories. CONCLUSIONS: The likely mechanism of pathogenesis involves cerebral oxygen gas embolization. The use of hyperbaric therapy should be considered in treating hydrogen peroxide poisoning.

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.

An unexpected complication following immunoadsorption with a staphylococcal protein A column.

Extracorporeal immune adsorption with staphylococcal protein A (SPA) columns can remove immune complexes and immunoglobulins in the treatment of a variety of diseases. We present the case of an elderly man with neuropathy associated with monoclonal gammopathy, treated by 3 on-line SPA procedures. At the completion of these treatments his neuropathy relapsed, progressing to near-total paralysis. Return to a baseline clinical status required several months. The reason for this severe relapse is not clear. Possible explanations include SPA activation of T-lymphocytes, with release of gamma interferon and increased antigen recognition, or removal of an antiidiotype control mechanism. We advise caution in the application of immunoadsorption to conditions in which it has not yet been evaluated.

A prospective study of physical trauma and multiple sclerosis.

During an eight year period 170 multiple sclerosis (MS) patients and 134 controls without physical impairment were followed closely to record all episodes of physical trauma and to measure their effect on exacerbation rate and progression of MS. There was a total of 1407 instances of trauma, which were sorted into various categories. Overall there was no significant correlation between all-traumas and disease activity. There was, however, a statistically significant negative correlation between traumatic episodes and exacerbations in 95 patients who had exacerbations during the programme, due primarily to less activity of the disease during a three month period following surgical procedures and fractures. Electrical injury had a significant positive association with exacerbation using a three month at-risk period, but there were no other significant positive correlations in any other category of trauma, including minor head injuries; there were no cases of head injury with prolonged unconsciousness. There was no linkage between the frequency of trauma and progression of disability. MS patients had two to three times more trauma than controls.

Concentration-dependent energy-transfer processes in Er(3+)-and Tm(3+)-doped heavy-metal fluoride glass.

The energy-transfer rate from the Er(3+)(4)I(13/2) level to the Tm(3+)(3)H(4) level (C(11')N(T)) in BaF(2)/ThF(4) fluoride glass is measured and calculated. The results can be used to determine whether rate equations can be used to predict energy-transfer rates.

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.

Stimulated emission and tunable gain from Rh(2+) ions in RbCaF(3) crystals.

Stimulated emission was detected in RbCaF(3):Rh(2+) crystals through the observation of power-dependent shortening of the fluorescence lifetime and narrowing of the emission band with a distinct threshold. In addition, single-pass gain was observed to be tunable between about 700 and 720 nm.

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.