Early use of interferon beta patients with multiple sclerosis.

In recent years, major advances have been made in the management of multiple sclerosis (MS) in the form of new disease-modifying therapies, the most widely used of which is interferon (IFN) beta. A growing body of evidence indicates that the beneficial effects of IFN beta are maximised if treatment is started as soon as possible after the diagnosis of MS, and if patients are given the highest possible dose. The argument in favour of early treatment is based primarily on the finding that the inflammation of the central nervous system characteristic of MS leads to irreversible axonal destruction starting very early in the course of the disease. Evidence that IFN beta should be given at high doses comes from preclinical and clinical studies showing that the effects of this drug are strongly dose-dependent. Three formulations of IFN beta are currently available for the treatment of MS: subcutaneous (s.c.) IFN beta-1a, intramuscular (i.m.) IFN beta-1a and s.c. IFN beta-1b. All are well tolerated, although IFN beta-1a appears to be less immunogenic than IFN beta-1b. IFN beta-1a, in s.c. formulation, has advantages over the other formulations in terms of convenience, and is approved for use at higher doses than i.m. IFN beta-1a.

Bilateral abductor vocal fold paralysis due to myasthenia gravis.

We report a case of bilateral abductor vocal fold paralysis due to myasthenia gravis in a 61-year-old man who presented with stridor requiring tracheostomy. The stridor had been preceded by several weeks' history of diplopia.

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

OBJECTIVE: To determine the effect of humanized monoclonal antibody against alpha4 integrin (reactive with alpha4beta1 integrin or very-late antigen-4) on MRI lesion activity in MS. METHODS: A randomized, double-blind, placebo-controlled trial in 72 patients with active relapsing-remitting and secondary progressive MS was performed. Each patient received two IV infusions of anti-alpha4 integrin antibody (natalizumab; Antegren) or placebo 4 weeks apart and was followed up for 24 weeks with serial MRI and clinical assessment. RESULTS: The treated group exhibited significantly fewer new active lesions (mean 1.8 versus 3.6 per patient) and new enhancing lesions (mean 1.6 versus 3.3 per patient) than the placebo group over the first 12 weeks. There was no significant difference in the number of new active or new enhancing lesions in the second 12 weeks of the study. The number of baseline-enhancing lesions (i.e., lesions that enhanced on the baseline scan) that continued to enhance 4 weeks following the first treatment was not significantly different between the two groups. The number of patients with acute MS exacerbations was not significantly different in the two groups during the first 12 weeks (9 in the treated group versus 10 in placebo) but was higher in the treatment group in the second 12 weeks (14 versus 3; p = 0.005). The study was not, however, designed to look definitively at the effect of treatment on relapse rate. Treatment was well tolerated. CONCLUSIONS: Short-term treatment with monoclonal antibody against alpha4 integrin results in a significant reduction in the number of new active lesions on MRI. Further studies will be required to determine the longer term effect of this treatment on MRI and clinical outcomes.

Implications of the 5-year CR FIRST trial. Sinemet CR Five-Year International Response Fluctuation Study.

Almost since the introduction of levodopa for Parkinson's disease (PD), its side effects have concerned clinicians. One strategy to avoid side effects has been to delay levodopa therapy; an alternative has been to use early therapy but to avoid fluctuations in plasma levodopa levels. This latter strategy led to the development of sustained-release carbidopa-levodopa, which was compared with immediate-release carbidopa-levodopa in the CR Five-Year International Response Fluctuation Study (FIRST), a 5-year multicenter study of early, levodopa-naive PD patients. The incidence of motor fluctuations was lower than expected for both groups, and patients receiving sustained-release carbidopa-levodopa fared better on the activities of daily living portion of the Unified Parkinson's Disease Rating Scale and on portions of the Nottingham Health Profile. The trial demonstrated the value of low-dose therapy, the lack of toxicity of this low-dose approach over 5 years in early PD.

[Development of a neurological score for the clinical evaluation of sylvian infarctions]. / Mise au point d'un score neurologique pour l'évaluation clinique des infarctus sylviens.

Among the main methodological problems raised by clinical trials in cerebral vascular accidents, one of the most serious is the lack of well-established and widely accepted criteria to evaluate the course of the disease. On the basis of published scores and of several trials carried on by us in three different centres during the last few years, we have developed a neurological score devised to reflect, as accurately as possible, deficits due to infarctions in the Sylvian territory, yet rapid and simple enough to provide an objective and reproducible rating. We report here the results of a prospective study concerning the inter-rater variations of the score from one centre to the other (inter-centre study) and within each centre (intra-centre study). These results have led us to withdraw three items with insufficient response rate and poor agreement, viz, "mental confusion", "visual field" and "sensory disorders". With the remaining 10 items the mean agreement between individual items varied from 85% to 90% and the global score agreement exceeded 90%. A study comparing our score with the Barthel index showed close correlation up to the autonomy threshold (Barthel index = 60) and divergent results beyond that point. The good agreement observed between inter-rater variations suggests that the score is reliable but does not inform on its sensitivity. In view of their relative independence, the neurological and the functional score should be regarded as complementary and should be used together as criteria of clinical assessment.

[Identification, evaluation and treatment of dementia patients in society]. / Identification, évaluation et traitement des malades déments dans la société.

Patients with "mild to moderate" dementia might improve with appropriate drug therapy whereas patients with "severe" dementia are generally considered to have an irreversible condition, providing acute metabolic disorders have been excluded and appropriate investigations have been performed to exclude neurological conditions that might be amenable to neurosurgery. Since it is unlikely that this type of patient will be referred to the hospital outpatient clinics, it is necessary to identify these patients in the community. For this purpose, authors have used the Abbreviated Mental Test. A comparison between two observers (nurse and doctor) has been made. Subsequently, a 6 symptoms check-list, as abbreviated form of the Crichton Royal Rating Scale for geriatric patients, was used in an open pilot study on 260 patients completing a 12 weeks treatment by dihydroergotoxine mesylate (codergocrine mesylate, Hydergine) 4.5 mg once a day. Although this was an open pilot study, it does show that it is possible to identify and treat patients with "mild to moderate" dementia in the community. A single dose formulation in the elderly has obvious advantages. In this study, compliance was excellent and 88% of the patients showed significant improvement using the suggested rating scales.

Migraine: definition and classification.

There are an enormous number of terms and classifications used in the field of headache and migraine. There is little general agreement and the situation is not helped by the introduction of new terminologies. An approach is suggested to overcome this problem based on the clinical characteristics of the patient. Until there are more definite markers of the different types of headaches, e.g. biochemical, physiological or pharmacological, this should obviate the need for yet further neurological debate.

Diverging trends in cerebrovascular disease and ischaemic heart disease mortality.

The trends in age adjusted and age and sex specific mortality rates for the period 1968-1980 are compared for ischaemic heart disease and cerebrovascular disease. For both sexes and at all ages over 45 the mortality rates for cerebrovascular disease have fallen significantly. However, the mortality rates for ischaemic heart disease are rising significantly for males aged 55-64 and females aged 45-64. The divergence in trend is particularly noticeable for females aged 45-64. Possible hypotheses are discussed explaining this divergence in trend between two cardiovascular diseases of assumed similar aetiology.

North West Thames registry of neurological disease.

A feasibility study has been carried out to determine whether a population-based registry of neurological disease can be established using the Hospital (Inpatient) Activity Analysis (HAA) records for England and Wales. The study provides a valuable opportunity to use and test the HAA system. The neurological disease chosen was the Guillain-Barré-Strohl syndrome (GBS), because it would be expected that most patients would be admitted to hospital, and recurrent attacks or chronicity are rare. In this study it has been demonstrated that, for GBS, a neurological registry, based on HAA records, provided an excellent source of data to measure the incidence of the disease and potentially any change of incidence over time. The proportion of coding errors was found to be under 5%.