For the past 2 decades, clinical and basic science researchers have gained significant insights into the molecular and genetic pathways associated with common forms of craniosynostosis. This has led to invaluable information for families and physicians in their attempts to understand the heterogeneity of craniosynostosis. Genetic mutations have been identified in the fibroblast growth factor receptors (FGFRs) as well as in other targets, including TWIST1, BMP, and RUNX2. Greater understanding of these and other pathways has led to the development of innovative approaches for applying medical therapies to the treatment of craniosynostosis, in particular by maintaining suture patency. In this article, the authors discuss the molecular pathophysiological mechanisms underlying various forms of craniosynostosis. They also highlight recent developments in the field of molecular craniosynostosis research with the hope of identifying targets for medical therapies that might augment the results of surgical intervention.
Jennifer Kosty and Timothy W. Vogel
Jennifer A. Kosty, Juan Mejia-Munne, Rimal Dossani, Amey Savardekar, and Bharat Guthikonda
Jacques Jean Lhermitte (1877–1959) was among the most accomplished neurologists of the 20th century. In addition to working as a clinician and instructor, he authored more than 800 papers and 16 books on neurology, neuropathology, psychiatry, and mystical phenomena. In addition to the well-known “Lhermitte’s sign,” an electrical shock–like sensation caused by spinal cord irritation in demyelinating disease, Lhermitte was a pioneer in the study of the relationship between the physical substance of the brain and the experience of the mind. A fascinating example of this is the syndrome of peduncular hallucinosis, characterized by vivid visual hallucinations occurring in fully lucid patients. This syndrome, which was initially described as the result of a midbrain insult, also may occur with injury to the thalamus or pons. It has been reported as a presenting symptom of various tumors and as a complication of neurosurgical procedures. Here, the authors review the life of Lhermitte and provide a historical review of the syndrome of peduncular hallucinosis.
Alexander Micko, Benjamin I. Rapoport, Brett E. Youngerman, Reginald P. Fong, Jennifer Kosty, Andrew Brunswick, Shane Shahrestani, Gabriel Zada, and Theodore H. Schwartz
Incomplete resection of skull base pathology may result in local tumor recurrence. This study investigates the utility of 5-aminolevulinic acid (5-ALA) fluorescence during endoscopic endonasal approaches (EEAs) to increase visibility of pathologic tissue.
This retrospective multicenter series comprises patients with planned resection of an anterior skull base lesion who received preoperative 5-ALA at two tertiary care centers. Diagnostic use of a blue light endoscope was performed during EEA for all cases. Demographic and tumor characteristics as well as fluorescence status, quality, and homogeneity were assessed for each skull base pathology.
Twenty-eight skull base pathologies underwent blue-light EEA with preoperative 5-ALA, including 15 pituitary adenomas (54%), 4 meningiomas (14%), 3 craniopharyngiomas (11%), 2 Rathke’s cleft cysts (7%), as well as plasmacytoma, esthesioneuroblastoma, and sinonasal squamous cell carcinoma. Of these, 6 (21%) of 28 showed invasive growth into surrounding structures such as dura, bone, or compartments of the cavernous sinus. Tumor fluorescence was detected in 2 cases (7%), with strong fluorescence in 1 tuberculum sellae meningioma and vague fluorescence in 1 pituicytoma. In all other cases fluorescence was absent. Faint fluorescence of the normal pituitary gland was seen in 1 (7%) of 15 cases. A comparison between the particular tumor entities as well as a correlation between invasiveness, WHO grade, Ki-67, and positive fluorescence did not show any significant association.
With the possible exception of meningiomas, 5-ALA fluorescence has limited utility in the majority of endonasal skull base surgeries, although other pathology may be worth investigating.
Joseph C. Serrone, Ryan D. Tackla, Yair M. Gozal, Dennis J. Hanseman, Steven L. Gogela, Shawn M. Vuong, Jennifer A. Kosty, Calen A. Steiner, Bryan M. Krueger, Aaron W. Grossman, and Andrew J. Ringer
Many low-risk unruptured intracranial aneurysms (UIAs) are followed for growth with surveillance imaging. Growth of UIAs likely increases the risk of rupture. The incidence and risk factors of UIA growth or de novo aneurysm formation require further research. The authors retrospectively identify risk factors and annual risk for UIA growth or de novo aneurysm formation in an aneurysm surveillance protocol.
Over an 11.5-year period, the authors recommended surveillance imaging to 192 patients with 234 UIAs. The incidence of UIA growth and de novo aneurysm formation was assessed. With logistic regression, risk factors for UIA growth or de novo aneurysm formation and patient compliance with the surveillance protocol was assessed.
During 621 patient-years of follow-up, the incidence of aneurysm growth or de novo aneurysm formation was 5.0%/patient-year. At the 6-month examination, 5.2% of patients had aneurysm growth and 4.3% of aneurysms had grown. Four de novo aneurysms formed (0.64%/patient-year). Over 793 aneurysm-years of follow-up, the annual risk of aneurysm growth was 3.7%. Only initial aneurysm size predicted aneurysm growth (UIA < 5 mm = 1.6% vs UIA ≥ 5 mm = 8.7%, p = 0.002). Patients with growing UIAs were more likely to also have de novo aneurysms (p = 0.01). Patient compliance with this protocol was 65%, with younger age predictive of better compliance (p = 0.01).
Observation of low-risk UIAs with surveillance imaging can be implemented safely with good adherence. Aneurysm size is the only predictor of future growth. More frequent (semiannual) surveillance imaging for newly diagnosed UIAs and UIAs ≥ 5 mm is warranted.
Rimal H. Dossani, Danielle Terrell, Jennifer A. Kosty, Robert C. Ross, Audrey Demand, Elizabeth Wild, Racheal Peterson, Laura B. Ngwenya, Deborah L. Benzil, and Christina Notarianni
The objective of this study was to evaluate whether there are disparities in academic rank and promotion between men and women neurosurgeons.
The profiles of faculty members from 50 academic neurosurgery programs were reviewed to identify years in practice, number of PubMed-indexed publications, Doctor of Philosophy (PhD) attainment, and academic rank. The number of publications at each academic rank was compared between men and women after controlling for years in practice by using a negative binomial regression model. The relationship between gender and each academic rank was also determined after controlling for clustering at the institutional level, years in practice, and number of publications.
Of 841 faculty members identified, 761 (90%) were men (p = 0.0001). Women represented 12% of the assistant and associate professors but only 4% of the full professors. Men and women did not differ in terms of the percentage holding a PhD, years in practice, or number of publications at any academic rank. After controlling for years in practice and clustering at the facility level, the authors found that men were twice as likely as women to be named full professor (OR 2.2, 95% CI 1.09–4.44, p = 0.03). However, when institution, years in practice, PhD attainment, h-index, and number of publications were considered, men and women were equally likely to attain full professorship (OR 0.9, 95% CI 0.42–1.93).
Data analysis of the top neurosurgery programs suggests that although there are fewer women than men holding positions in academic neurosurgery, faculty rank attainment does not seem to be influenced by gender.
Devon LeFever, Audrey Demand, Sandeep Kandregula, Alexis Vega, Breydon Hobley, Soleil Paterson, Krystle Trosclair, Richard Menger, Jennifer Kosty, and Bharat Guthikonda
There are approximately 85,000 lawsuits filed against medical practitioners every year in the US. Among these lawsuits, neurosurgery has been identified as a “high-risk specialty” with exceptional chance of having medical malpractice suits filed. Major issues affecting the overall medicolegal environment include tort reform, the formation of medical review panels, the increasing practice of defensive medicine, and the rising costs of medical insurance. In this study, the authors provide a concise update of the current medicolegal environments of the 50 states and provide a general guide to favorable and unfavorable states in which to practice neurosurgery.
Data were acquired related to state-by-state medical review panel status, noneconomic damage caps, economic damage caps, and civil suit filing fees. States were placed into 5 categories based on the status of their current medicolegal environment.
Of the 50 states in the US, 18 have established a medical review panel process. Fifteen states have a mandatory medical review process, whereas 3 states rely on a voluntary process. Thirty-five states have tort reform and have placed a cap on noneconomic damages. These caps range from $250,000 to $2,350,000, with the median cap of $465,900. Only 8 states have placed a cap on total economic damages. These caps range from $500,000 to $2,350,000, with the median cap of $1,050,000. All states have a filing fee for a medical malpractice lawsuit. These costs range from $37 to $884, with the median cost for filing of $335.
Medicolegal healthcare reform will continue to play a vital role in physicians’ lives. It will dictate if physicians may practice proactively or be forced to act defensively. With medicolegal reform varying greatly among states, it will ultimately dictate if physicians move into or away from certain states and thus guide the availability of healthcare services. A desirable legal system for neurosurgeons, including caps on economic and noneconomic damages and availability of medical review panels, can lead to safer practice.