Peculiarities of Neurological Disorders and Study Designs

Background: Neurological disorders are heterogeneous clinical conditions with variable course and outcome. Summary: The basic aspects of the commonest neurological disorders are addressed along with the proposed structure of randomized clinical trials (RCTs). Dementing disorders, including Alzheimer's disease (AD), are clinical conditions in which altered cognitive functions are associated with behavioral and personality changes. Parkinson's disease (PD) is a multisystem disorder characterized by motor dysfunction associated with dysautonomia, sleep and olfactory disturbances, cognitive changes, and depression. Amyotrophic lateral sclerosis (ALS) is an invariably fatal clinical condition involving motor neurons. The available treatments are purely symptomatic for PD but virtually ineffective for AD and ALS. Headache disorders, multiple sclerosis, and epilepsy, three diseases characterized by recurrent symptoms and chronic or episodic course, can be fairly easily controlled by current treatments, but cannot be prevented nor cured. The objectives of treatments of neurodegenerative disorders include primary prevention, slowing or arrest of disease progression, and control of symptoms. Stroke is an acute clinical condition causing frequent disability and death, with only one approved treatment. There are many challenges to acute stroke clinical trials; among them, the very short therapeutic window and the issue of stroke heterogeneity. In this chapter, only the core elements of the study designs are outlined. Key Messages: The design of an RCT must be adapted to the basic characteristics of each clinical condition.