This chapter examines the rational, therapeutic potential, strategies, and obstacles to the delivery of neurotrophic factors using gene therapy for the treatment of neurologic diseases. Two general approaches are used for gene therapy. In ex vivo approaches, cells are genetically modified in vitro to express relevant genes, and then delivered to target areas. The chapter reviews the application of neurotrophic factor gene therapy to animal models of selected neurologic diseases, in which clinical applications are being investigated. In order to maximize the effectiveness of neurotrophic factors, other components of growth factor signaling pathways such as receptor expression can also be targeted. Even if neurotrophic factors are found to protect against degenerative processes in humans, these protective effects may be unrelated to underlying disease pathophysiology. As a result, there may be continued degeneration that negates any protective effects over time.

Rapid developments in molecular genetics in recent years have afforded tremendous growth in our understanding of the pathophysiology of many neurologic diseases. This chapter addresses the basis of the complexity in the genetic contributions to common neurologic disorders, gene-environment interaction, and the pathway for investigating the genetic contributions to disease risk. It describes the methods for collection of accurate information on disease occurrence in families, and research strategies commonly employed in genetic epidemiology. In general, complex diseases are much more common than simple genetic diseases. Some examples in neurology would include (among many others): epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), migraine, essential tremor, and amyotrophic lateral sclerosis (ALS). Variable expressivity is sometimes observed even in so-called simple genetic diseases. The genetic epidemiology of epilepsy provides a clear example of etiologic heterogeneity. Some genetic influences on susceptibility to complex diseases may involve genetic interaction (epistasis).

This chapter highlights the current issues in the epidemiology of brain tumors. It describes the classification of brain tumors in epidemiologic studies, the spatial and temporal occurrence of brain tumors, and the risk factors for brain tumors. Metastatic tumors of the brain may be derived from many primary sites and are of clinical significance because of seizures and other neurologic symptoms. The geographic patterns of brain tumor incidence and mortality rates are relatively stable as is found in many other neurologic diseases such as amyotrophic lateral sclerosis (ALS) and idiopathic epilepsy. Traumatic brain injury has long been considered a risk factor for intracranial neoplasia, especially meningioma. The tumors are then usually demonstrated by magnetic resonance imaging (MRI). The onset of seizure in people aged 35-64 must first be evaluated for benign or malignant brain tumor.