Prognostic categories for amyotrophic lateral sclerosis.

Our objective was to generate a prognostic classification method for amyotrophic lateral sclerosis (ALS) from a prognostic model built using clinical variables from a population register. We carried out a retrospective multivariate analysis of 713 patients with ALS over a 20-year period from the South-East England Amyotrophic Lateral Sclerosis (SEALS) population register. Patients were randomly allocated to 'discovery' or 'test' cohorts. A prognostic score was calculated using the discovery cohort and then used to predict survival in the test cohort. The score was used as a predictor variable to split the test cohort in four prognostic categories (good, moderate, average, poor). The accuracy of the score in predicting survival was tested by checking whether the predicted survival fell within the actual survival tertile which that patient was in. A prognostic score generated from one cohort of patients predicted survival for a second cohort of patients (r(2) = 0.72). Six variables were included in the survival model: age at onset, diagnostic delay, El Escorial category, use of riluzole, gender and site of onset. Cox regression demonstrated a strong relationship between these variables and survival (χ(2) 80.8, df 1, p < 0.0001, n = 343) in the test cohort. Kaplan-Meier analysis demonstrated a significant difference in survival between clinical categories (log rank 161.932, df 3, p < 0.001), and the prognostic score generated for the test cohort accurately predicted survival in 64% of the patients. In conclusion, it is possible to correctly classify patients into prognostic categories using clinical data easily available at time of diagnosis.

Amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence (average 1.89 per 100,000/year) and prevalence (average 5.2 per 100,000) are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M:F ratio approximately 1.5:1). Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1-2 years. Paralysis is progressive and leads to death due to respiratory failure within 2-3 years for bulbar onset cases and 3-5 years for limb onset ALS cases. Most ALS cases are sporadic but 5-10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2-5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease) by appropriate investigations. The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43 immunoreactive inclusions in degenerating lower motor neurones. Signs of upper motor neurone and lower motor neurone damage not explained by any other disease process are suggestive of ALS. The management of ALS is supportive, palliative, and multidisciplinary. Non-invasive ventilation prolongs survival and improves quality of life. Riluzole is the only drug that has been shown to extend survival.