ABSTRACT
It is particularly difficult to discuss the prognosis with an individual who has just been diagnosed with amyotrophic lateral sclerosis (ALS). Indeed, this task has been made especially challenging in the light of current knowledge that ALS is not a homogeneous clinicopathological entity but rather encompasses a spectrum of related disorders each with different presentations and rates of progression. This chapter reviews the behavior of ALS in its ‘‘natural,’’ untreated state, and not only compares clinical subtypes but also assesses various factors that significantly impact rates of progression, patterns of spread, and survival. The data so presented allow a greater degree of accuracy when discussing prognosis but it is important to realize that it is probably not possible to gain an absolutely accurate picture of the natural history of ALS for any one individual: many variables are difficult to assess either in clinics or in research trials including epigenetic influences, the environment, mental state, personality, cognitive function, diet, copathologies, and the use of medications. The mode of data collection has varied considerably across the many studies that have commented upon survival rates, rates of progression, and clinical progression patterns in ALS. Older studies were retrospective reviews of rather mixed patient populations containing sporadic and familial cases along with ALS variants such as progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), and various other motor neuron disorders. One would think that the introduction of consensus criteria for the classification and diagnosis of ALS might have smoothed out such issues in modern studies but the accuracy of conclusions based upon post hoc analysis of even the most rigorously compiled modern ALS databases has also been the subject of debate (1-4). Furthermore, modern natural history studies must now account for the fact that some patients are receiving riluzole, which is itself an independent prognostic factor for survival. Moreover, many patients are treated with antioxidants such as vitamins C and E and/or receive interventions that may improve survival such as percutaneous gastrostomy and non-invasive positive pressure ventilation. As a consequence, it has become increasingly difficult, if not impossible, to perform true ‘‘natural’’ history studies (5-9).
