A Fandango of Form and Function: The Interplay Between Clinical Neurology and Neuropathology Evaluation

Abstract

The central (CNS) and peripheral (PNS) nervous systems of vertebrates represent divisions of a continuous, body-wide communication grid based on conserved principles of structural organization. Discrete neuroanatomic regions within this grid are associated with specific neural functions, so distinct patterns of neurological dysfunction (“problems”) can provide guidance regarding neural regions to evaluate beyond those in published sampling schemes or institutional standard operating procedures. Each neurological problem or syndrome (i.e., a group of in-life signs indicating that a given neuroanatomic region is damaged) is associated with a particular list of differential diagnoses and causes. Vulnerability of neural cells and tissues is influenced by intrinsic tissue properties (e.g., high metabolic rates of neurons, presence of blood:tissue barriers, degree of collateral vascular supply) and extrinsic factors (bone protuberances and connective tissue partitions impinging on neural surfaces, fluid flow patterns in the cerebroventricular system and meninges, etc.). In the toxicologic pathology setting, expansion (when warranted) of routine neural sampling protocols to collect additional anatomic regions correlated to a specific neurological problem improves the likelihood that a neuropathological evaluation will identify lesions and causes responsible for neurological conditions as well as detect findings related to potential test item-related neurotoxicity.