Tumors of the spine are a heterogeneous group of neoplasms involving the spinal column and spinal cord. They can be distinguished based on their location within the spine into three groups: intradural–intramedullary, intradural–extramedullary, and extradural. Another classification seeks to separate out these tumors based on their cell of origin, with primary spine tumors arising from either the spinal cord itself, its surrounding coverings including the leptomeninges, bone, cartilage, and soft tissue, or as secondary tumors arising from spinal involvement of a systemic neoplasm such as myeloma or as a metastasis from a distant site. This chapter seeks to discuss current evidence on the genetic, epigenetic, and cellular underpinnings of spine tumors with emphasis on the pathobiology and mechanisms underlying these neoplasms.

We discuss the fundamental units of the nervous system: neurons and supporting cells, which are formed from radial glial cells, progenitor cells that divide to generate new neurons, which then migrate to their destination. An understanding of the anatomy of neurons and their function enables us to decipher how information travels within the nervous system and how neurons communicate with each other through synapses to form networks capable of performing sophisticated and complex tasks. We then discuss how ions traverse the cell membrane and the critical role ion channels play in establishing resting membrane potential, and how action potentials are generated and propagated along the axon.

Spondylolisthesis is defined as the slippage of one vertebra over another. When the posterior bony elements are dissociated from the anterior column, high shear forces on the disc can lead to slippage of the vertebral bodies on one another. There are five types: dysplastic isthmic, degenerative, traumatic, and pathological. Biomechanical models are limited and attempt to replicate on isthmic and degenerative etiologies. From a clinical standpoint, several studies have explored the relative efficacy of surgical versus non-operative treatment and among surgical treatments, the need for decompression and fusion vs decompression alone. While several landmark studies have established several guides to surgical treatment, the lack of consensus on the use of different surgical approaches leaves room for future work.

Pediatric vascular malformations are a heterogeneous group of disorders that can generally be categorized into structural lesions and arteriopathies. The most common structural lesions encountered in pediatric neurosurgery include high-flow malformations involving abnormal connections between arteries and veins and low-flow malformations of aberrant capillary development(cavernous malformations). The term “moyamoya” is used to encompass a diverse group of arteriopathies characterized by the shared finding of progressive stenosis of the intracranial internal carotid arteries resulting in stroke. Here we will define these lesions, discuss epidemiology to put the scope of the disease in context, and then review the pathobiology in detail, with current genetic screening recommendations.

Neurosurgeons have the privilege of peeking inside the most precious and the most mysterious device on earth: the human brain. The human brain is also the most expensive device on earth given that mental health problems constitute the largest health care cost. By deciphering the inner secrets of brain computations, scientists and engineers have taken inspiration to develop smart artificial intelligence(AI) algorithms. These AI algorithms in turn provide much help to understanding brain function and to multiple applications in brain disorders, including neurosurgery.

The peripheral nervous system(PNS) comprises spinal and cranial nerves, which include motor, sensory, and autonomic nerves, as well as their roots, trunks, plexuses, ganglia, and accompanying supportive connective tissue distal to the brain and spinal cord. It is located peripheral to the central nervous system(CNS), and has very little in the way of protection from injury. In contrast to the CNS, it has a much higher innate capacity for repair and recovery after injury. Despite its physiological diversity, the PNS has a highly organized and choreographed injury response mechanism partially explaining its improved outcomes post-injury. In this chapter, we discuss the pathophysiology of peripheral nerve injury(PNI) and its ensuing reparative response. Before delving into PNIs and their classifications, it is important to review the basic anatomic organization of the PNS, its key cellular components, and supporting connective tissue.

Spinal cord injury(SCI) is a debilitating problem with a global incidence of 8–246 cases per million and an associated significant increase in healthcare cost. Research generally focuses on two broad categories: minimizing initial insult via modulation of primary and secondary injury cascades, or on novel therapeutic strategies aimed at recovering function. To this end, numerous SCI preclinical models have been developed, and promising clinical trials have arisen as a result, highlighting the importance of choosing the optimal model in relation to one’s scientific question. We highlight relevant spinal cord anatomy, embryology, and the pathophysiology of SCI with a focus on how these factors relate to preclinical models of SCI and spinal cord trauma, and hope to highlight important factors necessary for future research.

The brain and the encased skull constitute an incompressible system that encloses a volume of approximately 1450 ml. Normally, the intracranial volume is made up of 80% brain tissue, 10% cerebrospinal fluid(CSF), and 10% intravascular blood. The basic principle of physics in relation to intracranial content is described by the Monroe–Kellie doctrine. This hypothesis states that the total volume of the brain, CSF, and intracranial blood should be constant. Any increases in the volume of one of the components must be at the expense of the other two to maintain adequate brain function.

Peripheral nerve injuries(PNIs) come in many varieties and their mechanism of injury can have a tremendous impact on a patient’s expected outcome. As discussed in Chapter 26, depending on the mechanism, PNIs have a relatively well-choreographed response to injury. However, much of this sequence will be influenced by both modifiable and non-modifiable prognostic factors. Furthermore, this mechanism of injury and its severity will also help dictate the appropriate treatment of the injury. In this chapter, basic science principles and models addressing PNIs are more specifically examined as they occur in the context of trauma, entrapment, tumors, and the changes occurring in acute and chronic pain states. Clinical case examples of such injuries will be discussed to conclude each section, including their respective management.

Radiculopathy refers to pathology at the nerve root level, manifest as positive symptoms such as pain, paresthesias and dysesthesias, and negative symptoms such as numbness and weakness. While a number of causes for radiculopathy exist, the archetypal etiology is lumbar disc herniation, leading to compression of the traversing or, less commonly, exiting nerve root. Such mechanical bases for radiculopathy were first recognized nearly a century ago, initially in the lumbar region by Mixter and Barr(1934),followed by the cervical spine by Semmes and Murphey in 1943.

Degenerative cervical myelopathy(DCM) is the most debilitating form of degenerative disc disease, and is the most common acquired cause of spinal cord dysfunction in adults. DCM is caused by progressive abnormalities of the vertebral column that result in spinal cord damage due to both primary mechanical and secondary biological injury. DCM pathohistology demonstrates a consistent pattern of deleterious changes including severe Wallerian degeneration cephalad and caudal to the level of compression, apoptotic oligodendrocyte cell loss, and anterior horn dropout. Spinal cord ischemia and hypoxia play a major role in DCM pathogenesis. Novel spinal cord imaging studies such as MR spectroscopy and diffusion tensor imaging have provided novel insights into the neurobiology of this disorder. The central nervous system effects of DCM not only involve the spinal cord, but also include upstream functional and structural alterations that can influence disease progression and response to surgical intervention.

A thorough knowledge of gross human neuroanatomy is important in understanding basic and clinical neuroscience. In this chapter we describe the key anatomical features of the human brain followed by a discussion on the main developmental processes and signaling mechanisms of neurogenesis and embryology. Finally, we introduce the reader to different model organisms commonly used in neuroscience research.

Brain tumors in adults and children range from devastating malignant tumors with a dire prognosis to benign tumors that can be totally resected with a favorable outcome. The incidence rate for primary brain tumors in adults in the United States is approximately 23.8 per 100,000 persons. Of those, approximately two thirds are benign or borderline in nature. The most common benign tumor in adults is meningioma. The incidence in the pediatric population is approximately 6.1 per 100,000 children. However, the incidence of malignant brain tumors is higher in children than adults. We discuss the most common benign brain tumors in adults followed by a discussion on pediatric brain tumors.

Hydrocephalus affects 1/1000 births and is treated using neurosurgical cerebrospinal fluid(CSF) diversion techniques with high complication and failure rates. Recent data on the pathogenesis of acute post-hemorrhagic hydrocephalus(PHH) have implicated an acute Toll-like receptor(TLR4)-dependent hypersecretory response of the choroid plexus epithelium(CPe), the site of highly regulated CSF production and part of the blood–CSF barrier. Post-infectious hydrocephalus(PIH) is the most common form of hydrocephalus worldwide and shares multiple features with PHH, including TLR4-regulated CSF cytokines and immune cells. We introduce the concept of “inflammatory hydrocephalus”, and argue this may more precisely convey the shared pathogenic mechanisms and potential therapeutic vulnerabilities of PHH/PIH than the current concept of “secondary hydrocephalus.” This change of emphasis could shift our view of PHH/PIH from that of lifelong neurosurgical disorders to one of preventable neuroinflammatory conditions. In addition to attenuating acute CPe hypersecretion, early targeting of TLR4 may prevent inflammation-induced brain damage resulting in scarring, obstruction, and poor long-term neurodevelopmental outcomes.

The immune system is a complex system that works to recognize and eliminate foreign antigens – any protein, carbohydrate, lipid, deoxyribonucleic acid, or small organic molecule that can produce an immune response – from the body, and is divided into two subdivisions: the innate immune system and the adaptive immune system.

Artificial intelligence(AI), a term first coined by John McCarthy in the 1950s, is best thought of as the design of intelligent agents that can recognize and process stimuli to make decisions, similar to humans. The use of AI and artificial neural networks(ANNs) in medicine has been widely adopted to improve the efficiency of diagnostic medicine, and these include ANN-based analysis of electrocardiograms, electroencephalograms, radiographs, and automated computerized systems based on ANNs for detection of cancer data.

Craniosynostosis is a condition associated with the pathologic premature fusion of one or more cranial sutures. Physiologically, the metopic suture closes in infancy, while the remaining sutures close years later, even into adulthood. In craniosynostosis, characteristic calvarial deformity first appears on ultrasound in the second trimester and precedes identifiable suture fusion by 4–16 weeks. When this premature closure occurs, it is associated with restriction of calvarial growth perpendicular to the fused suture, with compensatory increase in growth at the remaining sutures. Previously there was debate as to whether the suture fusion itself drives this restriction of growth, or whether a cranial base deformity drives the abnormal development through tension bands in the dura. Currently there is a preponderance of evidence from human and rabbit studies supporting the idea that suture fusion is at least a significant contributor to the overall skull shape abnormality. The natural history of the disease is such that the deformity observed in infancy increases in severity if not surgically corrected.

Vascular neurosurgery is a diverse field focused on surgical and interventional treatment of cerebrovascular disease. Given this diverse disease pool vascular neurosurgery spans multiple fields, including neurology, cardiology, intensive care, interventional radiology, and clinical genetics and can affect involve both adult and pediatric patents. Despite extensive basic and translational research into the pathophysiology of cerebrovascular disease very few treatments have been successfully implemented into clinical practice. In this chapter we review the animal models used in the study of the pathophysiology of subarachnoid hemorrhage and its sequelae, such as early brain injury and delayed cerebral ischemia, highlighting the challenges and future direction. Furthermore, we will also discuss the animal models used to elucidate the mechanisms behind aneurysm formation.