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Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Coronal brain slices allow the study of neurotoxicity and "neuroprotection" under conditions where the differentiation-state and interrelationships of the neurones and glial cells are closer to those occurring in the intact tissue than is the case for co-cultured cell systems. The involvement of glial cells in the excitotoxicity of kainate and the potentiation of this toxicity by inhibition of glutamine synthase can be demonstrated. Longer-term toxicity of kainate may also be compounded by depletion of glutathione levels resulting from inhibition of gamma-glutamylcysteine synthase. The involvement of nitric oxide formation in the toxicity of N-methyl-D-aspartate can also be shown. The neurotoxicity of 1-methyl-4-phenylpyridinium can be readily demonstrated in coronal slice preparations. Taurine affords protection against this neurotoxicity. The possible mechanisms of these effects are considered in terms of the cyclic interrelationships between the different events which can lead to cell death.

Forty-five patients with Wilson's disease (WD) were prospectively studied: 27 had neurological deficits, 12 hepatic signs, and 6 were asymptomatic. Kayser-Fleischer rings occurred in 23 of the neurological patients and in only 4 of the hepatic patients. Neurological features were extremely variable with respect to frequency and severity. Most frequent were dysdiadochokinesis (25 patients), dysarthria (23), bradykinesia (17), and posture tremor (14). Fifteen, mainly long-term treated patients, presented with rather discrete neurological abnormalities which predominantly consisted of dysarthria and various forms of tremor. Eight patients had a parkinsonian type of neurological WD associated with signs of an organic mood syndrome. Three patients were predominantly hyperkinetic, presenting with dystonic and choreatic movements. In 1 patient, ataxia was the predominant neurological feature. There was a clear-cut correlation between the severity of neurological impairment and the restriction in functional capacity. Nine patients were not able to engage in salaried employment or were retired. Psychiatric symptoms and behavioural disorders were common, varying from mild personality and psychological disturbances to severe psychiatric illness resembling psychotic disorders and major depressive syndromes. Significant mental deterioration was not found in the patients. Disturbances of mood were observed in 12 patients, all of whom had neurological abnormalities. There was a history of an attempted suicide in 7 patients, and a history of an organic delusional syndrome in 3.