Pediatric Pseudotumor Cerebri Syndrome: Recent Insights and Future Directions

Pediatric pseudotumor cerebri syndrome (PTCS) is an emerging disease worldwide because of the rise of pediatric obesity in both western and poorer countries. It is important that pediatricians and pediatric neurologists fully appreciate PTCS, so that timely and correct diagnoses can minimize permanent visual impairment in both young and adolescent children. Prepubertal PTCS is often secondary to different causes and comorbidities, in contrast to the adult PTCS that is usually primary (idiopathic). Additionally, studying clinical characteristics of PTCS in the pediatric age group offers new possibilities to understand the disease by comparing manifestations at various developmental ages versus adults.

This special issue focuses on PTCS pathophysiology particularly. Significantly, the actual molecular physiology basis for the elevated cerebrospinal fluid (CSF) pressure is unknown. Therefore, researchers should consider placing top priority on elucidating biochemical and functional mechanisms that lead to elevated CSF pressure with its consequent papilledema and optic nerve damage. Recent research perspectives shed new light on possible mechanisms that underlie PTCS. Encouraging leads implicate endocrine-metabolic derangements as a contributing factor to impaired CSF dynamics. In addition, the research area of bioenergetic-hormonal mechanisms, involving choroid plexus and other transport interfaces, holds promise for providing fresh insights on the molecular etiology of PTCS.

Pediatric PTCS follows different childhood conditions and pathologies, for example, nephrologic, rheumatologic, and infectious states. Accordingly, this special issue emphasizes the involvement of several pediatric subspecialties for clinically assessing children with PTCS. Pediatric specialists in neurology, nephrology, and endocrinology have all made important contributions to this issue on PTCS in young children and teenagers. It is becoming increasingly evident that prepubertal and adolescent patients should be differentiated in terms of how pediatric PTCS is displayed according to clinical criteria. Adolescence, with its hormonal surges and weight gains, is characterized by a PTCS state closer to adulthood than prepuberty. Such differences may shed light on the role of hormones and metabolites in promoting PTCS in obese versus nonobese individuals.

A multidisciplinary approach to PTCS is required across different medical specialties. Thus, ophthalmologists, pediatricians, and neurosurgeons have valuable roles in clinically assessing and managing children with PTCS. Advances in magnetic resonance imaging technology and spectral domain optical computed tomography, as well as more effective use of ultrasonography, are at the forefront in enabling more effective diagnoses of young patients with PTCS. A greater use of genetic analyses and familial genotypes, combined with a deeper probing of metabolic-hormonal states, will add new dimensions to the diagnosis and management of PTCS.

Clearly, there is a great pharmacologic need for new agents to stabilize or eliminate PTCS in children as well as in adults. Acetazolamide and corticosteroids have been the mainstay for PTCS pharmacotherapy for several decades. However, these agents have limited efficacy and a wide array of undesirable side effects. Before new therapeutic agents can be identified, however, pharmacologic targets need to be identified. Several potential targets are addressed in these studies on PTCS: (1) choroid plexus formation of fluid (possible hypersecretion), (2) arachnoid under-reabsorption of CSF (due to increased resistance to outflow), (3) cerebral edema (reduced brain compliance), and (4) elevated cerebral venous pressure.

Fluid dynamic models that integrate these four pathophysiologic factors need to be developed in both clinical and experimental settings. Acquiring such information will expedite the development of novel drugs to treat PTCS, thereby bringing this field into the arena of molecular medicine.

This special issue was only possible thanks to the work of all contributors and international authorities who wrote the papers. Each author has helped identify present pediatric PTCS issues and progress and/or what still needs to be done to advance the cause. Our collective goal is a unified approach, clinicians with basic researchers, for relieving PTCS children suffering to enable a more enjoyable quality of life.