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Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality. We identified the subjects from the computer database of the government hospital system between 1 January 1997 and 31 January 2002 by searching the ICD code starting from 335.xx. Every retrieved case or their records were reviewed and validated by neurologist(s) of the responsible regional hospitals which the patients attended. One hundred and twenty cases from seven regional hospitals (serving 48.05% of the HKSAR population) were identified, validated and confirmed to be MND or related diseases. Ninety-eight new cases were diagnosed during the study period. Average age of onset was 58.76 years; SD 14.12 (28-89) years. Male to female ratio was 1.72:1. Peak age of onset was 60-64 years without sex difference. The adjusted incidence rate was 0.60/100,000/year. The adjusted point prevalence at the prevalence date (31 January 2001) was 3.04/100,000. Despite the incidence and prevalence of MND among Hong Kong Chinese, it remained low compared to worldwide figures, and our data suggested a significant rise of MND or related disease in the last decade. A territory-wide prospective epidemiological study is indicated.

Background: Riluzole 100 mg probably prolongs survival in patients with amyotrophic lateral sclerosis by about two months and the safety of the drug is not a major concern. The evidence from randomized controlled trials indicates that patients taking riluzole probably survive longer than patients taking placebo. The beneficial effects are very modest and the drug is expensive. Adverse effects from riluzole are relatively minor and for the most part reversible after stopping the drug. Riluzole has been approved for treatment of patients with amyotrophic lateral sclerosis in many countries but not all. Questions persist about its clinical utility because of high cost, modest efficacy and concern over adverse effects., Objectives: To examine the efficacy of riluzole in prolonging survival, and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival., Search Strategy: Search of the Cochrane Neuromuscular Disease Group Register for randomized trials and enquiry from authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. The most recent search was November 2002., Selection Criteria: Randomized trials of adults with diagnosis of amyotrophic lateral sclerosis (ALS), treated with riluzole or placebo. Types of outcome measures: Primary: pooled hazard ratio of tracheostomy-free survival over all time points with riluzole 100 mg. Secondary: per cent mortality as a function of time with riluzole 100 mg and other doses of riluzole; neurologic function, quality of life, muscle strength and adverse events., Data Collection & Analysis: We identified four eligible randomized trials. Each reviewer graded them for methodological quality. Data extraction was performed by a single reviewer and checked by two others. We obtained some missing data from investigators and regulatory agencies. We performed meta-analyses with Review Manager 4.1 software using a fixed effects model. A test of drug efficacy was based on the Parmar pooled hazard ratio., Results: The three trials examining tracheostomy-free survival included a total of 876 riluzole treated patients and 406 placebo treated patients. The data for tracheostomy-free survival was not available from the fourth trial. The methodological quality was acceptable and the three trials were easily comparable, although one trial included older patients in more advanced stages of amyotrophic lateral sclerosis. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (p=0.039, hazard ratio 0.80, 95% confidence interval 0.64 to 0.99) and there was no evidence of heterogeneity (p=0.33). When the third trial (which included older and more seriously affected patients) is added, there is evidence of heterogeneity (p<0.0001) and the random effects model, which takes this into account results in the overall treatment effect estimate falling just short of significance (p=0.056, hazard ratio 0.84, 95% confidence interval 0.70 to 1.01). This represents a 9% gain in the probability of surviving one year (57% in the placebo and 66% in the riluzole group). In secondary analyses of survival at separate time points, there was a significant survival advantage with riluzole 100 mg at six, nine, 12 and 15 months, but not at three or 18 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. There were no data on quality of life, but patients treated with riluzole remained in a more moderately affected health state significantly longer than placebo-treated patients (weighted mean difference 35.5 days, 95% confidence interval 5.9 to 65.0). A threefold increase in serum alanine transferase was more frequent in riluzole treated patients than controls (weighted mean difference 2.69, 95% confidence interval 1.65 to 4.38)., Conclusions: Riluzole 100 mg daily is reasonably safe and probably prolongs survival by about two months in patients with ALS. More studies are needed, especially to clarify its effect in older patients (over 75 years), and those with more advanced disease.

Objective: To evaluate the clinical application of non-invasive ventilation (NIV) in motor neuron disease (MND) in the UK., Method: We conducted a postal survey of the current clinical practice of all consultant neurologists in the UK, with a second mailing to non-responders after 6 weeks. The principal outcome measures assessed were: 1. the percentage of patients with MND receiving NIV, 2. access to a NIV service, 3. routine monitoring of respiratory function, and 4. influence of symptoms, respiratory function, rate of disease progression, level of disability and bulbar involvement on referral for NIV., Results: The response rate was 76%, 1719 new patients had been diagnosed in the preceding 12 months and a total of 2280 patients were under review. Of these, 126 were currently receiving NIV (5.5% of patients under review, estimated 2.6-3.5% of all MND patients). Most neurologists (172/265) had referred no patients for NIV in the preceding year, while three neurologists made 30% of all referrals nationally. Referral was based primarily on symptoms, and was influenced by the number of MND patients under review, level of disability, rate of disease progression and availability of a NIV service. Bulbar involvement was considered a relative contra-indication to NIV by 51% of responders., Conclusions: In the UK, few patients with MND are treated with NIV. There is marked variation in clinical practice. This may reflect uncertainty about the role of non-invasive ventilation in MND, and emphasizes the need for a randomized controlled trial to assess the impact of NIV on quality of life and survival.

Patient-specific (endogenous) and population-specific (exogenous) risk factor analysis is identifying novel physical and chemical exposures which might be time-linked to the development of amyotrophic lateral sclerosis (ALS) and other motor neuron diseases. Electric injury in a number of case-control studies as well as prolonged exposure at work and home to agricultural chemicals in pesticides and herbicides have been identified as significant risk factors. Heavy exercise, trauma with or without bone fractures and heavy metal exposure at work have not been confirmed as risk factors. Surprisingly, occupation as a pilot or navigator has recently been identified as a potential risk factor, which will need to be confirmed. The introduction of international patient registries in North America (ALS CARE) and in Europe (ALS HPS) will facilitate future studies on the prognosis of ALS, adherence to standards of practice, quality of life and patient outcome studies. An initial survey of the ALS Patient Care Database in January 1999, when nearly 1800 patients had been entered across North America, indicated the median time from ALS onset to diagnosis is 14 months when no second opinion is requested, 12 months if the patient requests a second opinion and 10 months when the neurologist requests an additional opinion. No significant difference was found in the median time to diagnose sporadic ALS patients compared with familial ALS patients.

Significant changes in the epidemiology of amyotrophic lateral sclerosis (ALS) have been observed over the last few years. Based on reports of studies from the 1970s and early 1980s, the incidence of ALS in Europe has been considered to be constant, with only slight differences in the incidence of ALS between different countries. However, flaws in the methodologies of these studies, such as case definition, case ascertainment, selection bias, study design and difficulties in the early diagnosis of cases, have been identified. More recent studies reveal a trend towards an increase in the ALS mortality rate over the past two decades, but the significance of this trend remains unclear. Recent ALS incidence studies, particularly those based on the 'register model', have given new insight into ALS epidemiology. ALS seems to be a uniform problem across Europe, with age-specific incidence rates showing a progressive increase up to the 70-79 age group. False-negative cases are frequent, ranging from 26-42% of cases. The rate of false-positive cases is approximately 10%. In approximately half of the false-positive cases, the possible diagnosis of ALS was withdrawn because the initial symptoms did not progress. No consistent epidemiological clues concerning the cause of ALS have been found in epidemiological studies. The only possible associations that perhaps warrant further investigation include farming, mechanical and electrical traumas, heavy labour and toxins or chemicals.

It is well known that the diagnostic process in amyotrophic lateral sclerosis (ALS) may be excessively prolonged, with negative consequences for the patients and their families. The ISIS study assessed the diagnostic process in 201 patients affected by ALS from 6 different countries (Argentina, Brazil, Germany, Italy, Spain and USA). The median time from onset to diagnosis ranged from 12 months in Spain to 17 months in Italy. The median time for patients to have a first consultation with a physician was 2 months (range: 1-1.5 months) and with a neurologist was 6-9 months. The median time needed for the neurologist to confirm the diagnosis was 3-6 months. Electromyography was performed on more than 90% of patients in all countries, and was requested in most cases by the neurologist. False-negative diagnoses were quite frequent (45% of cases with at least one other diagnosis evoked at any time before the ALS diagnosis) and were made by neurologists in 28% of cases, by general practitioners in 29% of cases, by orthopaedic surgeons in 26% of cases and by other specialists in 18% of cases. The reasons for misdiagnoses were: presence of other diseases to which the symptomatology was attributed, misinterpretation of examinations, and lack of familiarity with ALS.