Isolated subependymal giant cell astrocytoma (SEGA) in the absence of clinical tuberous sclerosis: two case reports and literature review.

PURPOSE: Subependymal giant cell astrocytoma (SEGA) is a WHO grade I pediatric glioma arising in 5-15% of patients with tuberous sclerosis (TSC). Rare cases of isolated SEGA without TSC have been described. The etiology, genetic mechanisms, natural history, and response to treatment of these lesions are currently unknown. We describe two such cases of isolated SEGA with follow-up. METHODS: Retrospective review was performed at a single institution to describe the clinical course of pathology-confirmed SEGA in patients with germline testing negative for TSC mutations. RESULTS: Two cases of isolated SEGA were identified. Genetic analysis of the tumor specimen was available for one, which revealed an 18 base pair deletion in TSC1. Both cases were managed with surgical resection, one with preoperative embolization. In spite of a gross total resection, one patient experienced recurrence after three years. Treatment with an mTOR inhibitor led to a significant interval reduction of the mass on follow-up MRI. The patient tolerated the medication well for 6 years and is now off of treatment for 2 years with a stable lesion. CONCLUSION: Cases of SEGA outside of the context of TSC are exceedingly rare, with only 48 cases previously described. The genetic mechanisms and treatment response of these lesions are poorly understood. To date, these lesions appear to respond well to mTOR inhibitors and may behave similarly to SEGAs associated with TSC. However, given that experience is extremely limited, these cases should be followed long term to better understand their natural history and treatment response.

The role of focused ultrasound for pediatric brain tumors: current insights and future implications on treatment strategies.

INTRODUCTION: Focused ultrasound (FUS) is an innovative and emerging technology for the treatment of adult and pediatric brain tumors and illustrates the intersection of various specialized fields, including neurosurgery, neuro-oncology, radiation oncology, and biomedical engineering. OBJECTIVE: The authors provide a comprehensive overview of the application and implications of FUS in treating pediatric brain tumors, with a special focus on pediatric low-grade gliomas (pLGGs) and the evolving landscape of this technology and its clinical utility. METHODS: The fundamental principles of FUS include its ability to induce thermal ablation or enhance drug delivery through transient blood-brain barrier (BBB) disruption, emphasizing the adaptability of high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU) applications. RESULTS: Several ongoing clinical trials explore the potential of FUS in offering alternative therapeutic strategies for pathologies where conventional treatments fall short, specifically centrally-located benign CNS tumors and diffuse intrinsic pontine glioma (DIPG). A case illustration involving the use of HIFU for pilocytic astrocytoma is presented. CONCLUSION: Discussions regarding future applications of FUS for the treatment of gliomas include improved drug delivery, immunomodulation, radiosensitization, and other technological advancements.

Clinical outcomes and complications of eyelid versus eyebrow approaches to supraorbital craniotomy: systematic review and indirect meta-analysis.

OBJECTIVE: Eyebrow supraorbital craniotomy is a versatile keyhole technique for treating intracranial pathologies. The eyelid supraorbital approach, an alternative approach to an eyebrow supraorbital craniotomy, has not been widely adopted among most neurosurgeons. The purpose of this systematic review and meta-analysis was to perform a pooled analysis of the complications of eyebrow or eyelid approaches for the treatment of aneurysms, meningiomas, and orbital tumors. METHODS: A systematic review of the literature in the PubMed, Embase, and Cochrane Review databases was conducted for identifying relevant literature using keywords such as "supraorbital," "eyelid," "eyebrow," "tumor," and "aneurysm." Eyebrow supraorbital craniotomies with or without orbitotomies and eyelid supraorbital craniotomies with orbitotomies for the treatment of orbital tumors, intracranial meningiomas, and aneurysms were selected. The primary outcomes were overall complications, cosmetic complications, and residual aneurysms and tumors. Secondary outcomes included five complication domains: orbital, wound-related, scalp or facial, neurological, and other complications. RESULTS: One hundred three articles were included in the synthesis. The pooled numbers of patients in the eyebrow and eyelid groups were 4689 and 358, respectively. No differences were found in overall complications or cosmetic complications between the eyebrow and eyelid groups. The proportion of residuals in the eyelid group (11.21%, effect size [ES] 0.26, 95% CI 0.12-0.41) was significantly higher (p < 0.05) than that in the eyebrow group (6.17%, ES 0.10, 95% CI 0.08-0.13). A subgroup analysis demonstrated significantly higher incidences of orbital, wound-related, and scalp or facial complications in the eyelid group (p < 0.05), but higher other complications in the eyebrow group. Performing an orbitotomy substantially increased the complication risk. CONCLUSIONS: This is the first meta-analysis that quantitatively compared complications of eyebrow versus eyelid approaches to supraorbital craniotomy. This study found similar overall complication rates but higher rates of selected complication domains in the eyelid group. The literature is limited by a high degree of variability in the reported outcomes.

Evolution of Surgical Management of Pineal Region Tumors in the Pediatric Population: A 17-Year Experience at a Single Institution.

INTRODUCTION: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients, and this is well demonstrated by our single institution's experience over a 17-year-period in which the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients will be outlined. METHODS: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children's National Hospital (CNH) from 2005 to 2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others. IRB approval was obtained (IRB: STUDY00000009), and consent was waived due to minimal risk to patients included. RESULTS: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). Twenty seven of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior interhemispheric (PIH, transcallosal) - used for 59.3% of the patients. Gross total resection was achieved in 50%; recurrence occurred in 20.9% and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011 to 2021. Most (73%) of the patients who received an ETV also underwent a concurrent endoscopic biopsy. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies. CONCLUSION: This series describes the evolution of surgical approaches and outcomes over a 17-year-period at a single institution. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. Though there has been a significant evolution in our understanding of and treatment for these tumors, in our series, the outcomes for these patients have not significantly changed over that time.

Outcomes of patients with nonepileptic transient neurologic symptoms after subdural hematoma evacuation.

BACKGROUND: Patients undergoing a subdural hematoma (SDH) evacuation can experience transient neurological symptoms (TNS) postoperatively. Electroencephalography (EEG) is used to rule out seizures. We aim to characterize patients with TNS and negative epileptiform activity on EEG and compare them to those with positive epileptiform EEG findings. METHODS: We performed a retrospective study of adult patients who underwent EEG for evaluation of TNS after undergoing SDH evacuation. Patients were stratified based on SDH type (acute and non-acute) and whether or not their EEG demonstrated positive epileptiform activity. A multivariate analysis was performed to identify predictors of negative EEG findings. RESULTS: One hundred twenty-nine SDH patients were included (45 (34.9%) acute; 84 (65.1%) non-acute). Overall, 45 (24 acute and 21 non-acute SDH patients) had positive epileptiform EEG findings, and 84 (21 acute and 63 non-acute SDH patients) had a negative EEG. Acute and non-acute SDH patients with positive EEG findings were more likely to suffer from greater than five episodes of TNS, impaired awareness, and motor symptoms, while the negative EEG group was more likely to suffer from negative symptoms. Non-acute SDH patients with positive EEG had longer mean ICU stays (14.6 vs. 7.2; p = 0.005). Both acute and non-acute SDH-positive EEG patients had worse disposition upon discharge (p < 0.05), worse modified Rankin score at discharge (p < 0.05), and 3-month follow-up (p < 0.05) and were more likely to be discharged on more than one antiepileptic drug (p < 0.001). CONCLUSION: Postoperative acute and non-acute SDH patients with TNS and negative EEG results are likely to have a favorable clinical picture. This distinction is therapeutically and prognostically important as these patients may not respond to typical antiepileptic drugs and they have better functional outcomes.

The Relationship Between Procedural Volume, Hospital Quality, and Postoperative Mortality in Pediatric Neurosurgery: Review of the Literature.

BACKGROUND: Studies of neurosurgical pediatric patients associate treatment at low-volume hospitals and by low-volume surgeons with increased odds of adverse outcomes. Although these associations suggest that increased centralization of care could be considered, we evaluate whether confounding endogenous factors mitigate against the proposed outcome benefits. METHODS: Literature review of English language articles from 1999 to 2021. We included articles that assessed volume-outcome effects in pediatric neurosurgical patients. RESULTS: Twelve papers were included from 1999 to 2021. Primary outcomes included mortality (9), length of stay (LOS) (6), complications (4), and shunt revision/failure rates (3). Volume was measured at the hospital level (8) and at the surgeon level (6). Four papers found that higher volume hospitals had lower odds of mortality. Two papers found that hospitals with higher volume had fewer complications. Two papers found that higher volume surgeons had decreased mortality (odds ratio [OR] 0.09-0.3). One paper found that high-volume surgeons had fewer complications (-2.4%; P = 0.006). After controlling for hospital factors (HF), two out of 7 analyses remained significant. Five analyses did not control for HF. CONCLUSIONS: The literature consistently demonstrates a relationship between higher hospital and surgeon volume and better outcomes for pediatric neurosurgical patients. Of the 7 articles that assessed HF, only 2 analyses found that surgical volume remained associated with better outcomes. No reports assessed the degree of centralization already present. The call for centralization of pediatric care should be tempered until variables such as hospital factors, distribution of cases, and clinical thresholds can be defined and studied.

Biomarkers related to hypertrophy of the ligamentum flavum: a systematic review of the literature.

OBJECTIVE: Spinal stenosis is one of the most common spinal disorders in the elderly. Hypertrophy of the ligamentum flavum (HLF) can contribute to spinal stenosis. The current literature suggests that various biomarkers may play important roles in the pathogenesis of HLF. However, the connection between these biomarkers and the development of HLF is still not well understood. This systematic review aims to explore the current literature on biomarkers related to the development of HLF. METHODS: A literature search was conducted using PubMed, Embase, Web of Science, and Cochrane Library. The search strategy looked for the titles, abstracts, and keywords of studies that contained a combination of the following phrases: "ligamentum flavum OR yellow ligament," "biomarkers," and "hypertrophy." Recorded data included study design, demographic characteristics (number of patients of each gender and mean age), study period, country where the study was conducted, biomarkers, and diagnostic modalities used. Risk of bias was assessed using the Newcastle-Ottawa Scale for case-control studies. RESULTS: The authors identified 39 studies. After screening, 26 full-text original articles assessing one or more biomarkers related to HLF were included. The included studies were conducted over a 22-year period. The most popular biomarkers studied, in order of frequency reported, were collagen types I and III (n = 10), transforming growth factor ß (TGF-ß) (n = 8), and interleukin (IL)-6 (n = 6). The authors found that mechanical stretching forces, tissue inhibitor of metalloproteinases 2 (TIMP-2) induction, and TGF-ß were associated with increased amounts of collagen I and III. IL-6 expression was increased by microRNA-21, as well as by leptin, through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. CONCLUSIONS: Biomarkers such as TGF-ß, IL-6, and collagen I and III have been consistently correlated with the development of HLF. However, the pathogenesis of HLF remains unclear due to the heterogeneity of the studies, patient populations, and research at the molecular level. Further studies are necessary to better characterize the pathogenesis of HLF and provide a more comprehensive understanding of how these biomarkers may aid in the diagnosis and treatment of HLF.

Awake transradial middle meningeal artery embolization and twist drill craniostomy for chronic subdural hematomas in the elderly: case series and technical note.

BACKGROUND: Due to prohibitive perioperative risk factors, optimal treatment for chronic subdural hematomas (cSDH) in the elderly remains unclear. Minimally invasive techniques are a viable option and include bedside subdural evacuation port system (SEPS), as well as prevention of recurrence with middle meningeal artery (MMA) embolization. We present a case series of elderly patients undergoing combined transradial MMA embolization and bed-side craniostomy as primary treatment for cSDH. METHODS: Patients 70 years and older from 2019 to 2020 that underwent single setting, awake transradial MMA embolization with concurrent SEPS placement under local anesthesia were included. Those with prior treatments, interventions performed under general anesthesia, or with less than 60-day follow-up were excluded. Descriptive analyses of baseline characteristics, radiologic parameters, comorbidities, and outcome measures were completed. RESULTS: Twenty elderly patients (mean age of 81.0 years) with multiple comorbidities underwent 28 MMA embolization+SEPS procedures as primary treatment for cSDH. Mean cSDH thickness was 1.8cm±0.6 cm with 7.3±3.9 mm midline shift. All patients tolerated the procedure well. 1/20 (5.0%) patients died within 30 days of the procedure. A majority of patients were discharged to home (12/20; 60.0%). There was an average of 3.6-month follow-up and one patient (5.0%) developed recurrence in the follow-up period requiring further intervention. CONCLUSIONS: In select elderly patients with high perioperative risk factors, primary treatment of cSDH using awake transradial MMA embolization+SEPS placement is a minimally invasive, feasible, and safe option. Further comparative studies are warranted to evaluate efficacy of the treatment.

Cirq robotic arm-assisted transpedicular instrumentation with intraoperative navigation: technical note and case series with 714 thoracolumbar screws.

The Cirq is a surgeon-controlled robotic arm that provides a new technique for accurately placing transpedicular screws. This report aims to present a technical report and our experience with this new robotic arm combined with intraoperative navigation. Technique and workflow using the Cirq robotic arm with intraoperative navigation is described. A retrospective review was conducted of all patients undergoing elective open thoracic/lumbar fusion surgery by a single surgeon in the first year of using the novel Cirq robotic arm. Descriptive analysis of patient and operative variables was performed. A total of 84 patients underwent placement of a total 714 transpedicular screws using the Cirq robotic arm. Most (69.1%) underwent 3-6 level fusion procedures. Mean operative time was 198 min total and 28 min when adjusted per screw. There was a learning curve with operative time per screw decreasing from 32 to 25 min from the first to second half of cases (p = 0.057). There were no intraoperative screw revisions and 2.4% (2/84) required instrumentation revision and return to the operating room. The Cirq robotic arm is seamlessly incorporated into the workflow of a transpedicular fusion. Our experience with over 700 pedicle screw placements using the Cirq robot demonstrates efficacy and safety although further comparative studies are needed.

Minimally Invasive Surgical Decompression without Fusion for the Treatment of Lumbar Synovial Cysts: Feasibility and Long-Term Outcomes.

BACKGROUND: Lumbar synovial cysts (LSCs) can cause painful radiculopathy and sensory and/or motor deficits. Historically, first-line surgical treatment has been decompression with fusion. Recently, minimally invasive laminectomy without fusion has shown equal or superior results to traditional decompression and fusion methods. OBJECTIVE: This study investigates the long-term efficacy of minimally invasive laminectomy without fusion in the treatment of LSC as it relates to the rate of subsequent fusion surgery. METHODS: A retrospective review was performed over a 10-year period of patients undergoing minimally invasive laminectomy for symptomatic LSCs. The primary end point was the rate of revision surgery requiring fusion. RESULTS: Eighty-five patients with symptomatic LSCs underwent minimally invasive laminectomy alone January 2010-August 2020 at our institution. The most common location was L4-5 (72%). Preoperative imaging identified spondylolisthesis (grade 1) in 43 patients (57%), none of which was unstable on available dynamic radiographs. Average procedure duration was 93 minutes, with 78% of patients discharged home on the same day of surgery. Over 46 months of mean follow-up, 17 patients (20%) required 19 revision operations. Of those operations, 16 were spinal fusions (17.6%). Median time to fusion surgery was 36 months. There were no identifiable risk factors on multivariate regression analysis that predicted the need for fusion. CONCLUSIONS: Minimally invasive laminectomy is an effective first-line treatment for symptomatic LSCs and avoids the need for fusion in most treated patients. Of our patients, 18% required a fusion over 46 months, suggesting that further studies are required to guide patient selection.

Microsurgical resection of previously embolized recurrent cerebellopontine angle AVM.

This is the case of a ruptured Spetzler-Martin grade II arteriovenous malformation (AVM) located in the cerebellopontine angle and draining into the transverse sinus. The AVM was initially treated with staged embolization using Onyx (ev3 Neurovascular). However, recurrence was noted and treatment with microsurgical resection was undertaken. The authors present technical nuances of the approach and strategies for microsurgical resection of a previously embolized recurrent AVM with the aid of intraoperative indocyanine green angiography. Follow-up after endovascular treatment is critical, and curative treatment with microsurgical resection can be achieved with low morbidity in such AVMs as demonstrated by this case. The video can be found here: https://youtu.be/LMpz_YTFC0g.

Perioperative Coronavirus Disease 2019 (COVID-19) Incidence and Outcomes in Neurosurgical Patients at Two Tertiary Care Centers in Washington, DC, During a Pandemic: A 6-Month Follow-up.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) continues to affect all aspects of health care delivery, and neurosurgical practices are not immune to its impact. We aimed to evaluate neurosurgical practice patterns as well as the perioperative incidence of COVID-19 in neurosurgical patients and their outcomes. METHODS: A retrospective review of neurosurgical and neurointerventional cases at 2 tertiary centers during the first 3 months of the first peak of COVID-19 pandemic (March 8 to June 8) as well as following 3 months (post-peak pandemic; June 9 to September 9) was performed. Baseline characteristics, perioperative COVID-19 test results, modified Medically Necessary, Time-Sensitive (mMeNTS) score, and outcome measures were compared between COVID-19-positive and-negative patients through bivariate and multivariate analysis. RESULTS: In total, 652 neurosurgical and 217 neurointerventional cases were performed during post-peak pandemic period. Cervical spine, lumbar spine, functional/pain, cranioplasty, and cerebral angiogram cases were significantly increased in the postpandemic period. There was a 2.9% (35/1197) positivity rate for COVID-19 testing overall and 3.6% (13/363) positivity rate postoperatively. Age, mMeNTS score, complications, length of stay, case acuity, American Society of Anesthesiologists status, and disposition were significantly different between COVID-19-positive and-negative patients. CONCLUSIONS: A significant increase in elective case volume during the post-peak pandemic period is feasible with low and acceptable incidence of COVID-19 in neurosurgical patients. COVID-19-positive patients were younger, less likely to undergo elective procedures, had increased length of stay, had more complications, and were discharged to a location other than home. The mMeNTS score plays a role in decision-making for scheduling elective cases.

Pituitary Apoplexy Case Series: Outcomes After Endoscopic Endonasal Transsphenoidal Surgery at a Single Tertiary Center.

BACKGROUND: The management of pituitary apoplexy, caused by acute hemorrhage and/or infarction of a pituitary adenoma, is debated. OBJECTIVE: To analyze clinical characteristics of patients undergoing endoscopic endonasal approaches (EEAs) for pituitary apoplexy. METHODS: A retrospective review of patients at our institution from 2012 to 2018 undergoing EEA for pituitary apoplexy diagnosed clinically and with imaging/pathologic findings. Analysis included demographics, symptoms, neuroendocrine deficits, neuroimaging, complications, symptom resolution, and follow-up details. RESULTS: Fifty patients (mean age, 53 years) were included. Preoperative symptoms included headache (86%), vision loss (62%), and cranial nerve paresis (40%). Mean tumor diameter was 2.7 cm and extrasellar extension was observed in 96% of tumors. Twenty-eight tumors were hemorrhagic (76%), 24 were necrotic (65%), and 13 (35%) had both features. Magnetic resonance imaging showed gross total resection in 58% of patients. Headache and vision loss improved in 87% and 86% of presenting patients. Cranial nerve paresis resolved in 72% of patients, partially improved in 11%, and remained unchanged in 17%. There were no deaths or carotid artery injuries. Surgical complications included postoperative cerebrospinal fluid leak (n = 4, 8%), epistaxis (n = 2, 4%), postoperative abscess (n = 1, 2%), and transient postoperative vision loss requiring reoperation (n = 1, 4%). Endocrinopathies improved in 21% of patients and panhypopituitarism persisted in 48% and developed in 6% of patients. Mean follow-up time was 26 months; 2 patients experienced recurrence. CONCLUSIONS: EEA for pituitary apoplexy is effective in rapidly improving headache and visual symptoms. Although neuro-ophthalmic deficits often improve over time, panhypopituitarism persists in most patients after surgical resection.

Outcomes Following Transsphenoidal Pituitary Surgery in the Elderly: A Retrospective Single-Center Review.

BACKGROUND: Transsphenoidal surgery (TSS) for pituitary adenomas (PAs) is performed on elderly patients with increasing frequency. More research is necessary to assess the risk factors that are associated with TSS in an aging population. OBJECTIVE: To perform a retrospective study on postoperative safety outcomes following TSS in the elderly population stratified by decade of life. METHODS: A retrospective chart review of the USC Pituitary Database was conducted to identify patients ≥70 yr, who underwent TSS for PAs between 1995 and 2017. Surgical outcomes were analyzed in elderly (≥70 yr) vs nonelderly (<70 yr) patients. Elderly patients were additionally stratified according to age 70 to 79 vs ≥80 yr. RESULTS: The cohorts included 115 elderly patients (70-79 yr: 94 patients; ≥80 yr: 21 patients) and 770 nonelderly patients. Elderly patients presented with more vision loss (62% vs 38%, P < .0001), dizziness (17% vs 6%, P = .0001) and altered mental status (7.3% vs 3%, P = .0451). Overall rates of surgical, medical, and endocrine complications were similar; however, elderly patients had significantly higher rates of postoperative hyponatremia (9.3% vs 4.7%, P = .0401) and lower rates of transient diabetes insipidus (0.9% vs 7.9%, P = .0038). Patients ≥ 80 yr had significantly more surgical complications (26.3%) compared to the 70 to 79 group (7.87%; P = .021) and <70 group (12.5%; P = .04). CONCLUSION: Patients >70 yr are appropriate surgical candidates for TSS given the similar safety outcomes as younger patients. Given the higher propensity for surgical complications; however, a higher level of operative selectivity should be maintained in octogenarian patients.

Dual responsive neurostimulation implants for epilepsy.

Closed-loop brain-responsive neurostimulation via the RNS System is a treatment option for adults with medically refractory focal epilepsy. Using a novel technique, 2 RNS Systems (2 neurostimulators and 4 leads) were successfully implanted in a single patient with bilateral parietal epileptogenic zones. In patients with multiple epileptogenic zones, this technique allows for additional treatment options. Implantation can be done successfully, without telemetry interference, using proper surgical planning and neurostimulator positioning.Trajectories for the depth leads were planned using neuronavigation with CT and MR imaging. Stereotactic frames were used for coordinate targeting. Each neurostimulator was positioned with maximal spacing to avoid telemetry interference while minimizing patient discomfort. A separate J-shaped incision was used for each neurostimulator to allow for compartmentalization in case of infection. In order to minimize surgical time and risk of infection, the neurostimulators were implanted in 2 separate surgeries, approximately 3 weeks apart.The neurostimulators and leads were successfully implanted without adverse surgical outcomes. The patient recovered uneventfully, and the early therapy settings over several months resulted in preliminary decreases in aura and seizure frequency. Stimulation by one of the neurostimulators did not result in stimulation artifacts detected by the contralateral neurostimulator.

Variability and Lack of Prognostic Value Associated With Atypical Pituitary Adenoma Diagnosis: A Systematic Review and Critical Assessment of the Diagnostic Criteria.

BACKGROUND: Atypical pituitary adenomas (APAs) are a subset of pituitary adenomas (PAs) characterized by the 2004 World Health Organization (WHO) guidelines to have higher risk histopathological features than typical PAs. In July 2017, the WHO published an update to their classification of pituitary tumors and abandoned the APA terminology. OBJECTIVE: To assess the prevalence and outcomes of patients diagnosed with APA through a literature review. Focus was placed on variation in the application of the previous WHO criteria and on rates of recurrence. METHODS: A systematic review of PubMed (2004-July 2017) was performed to identify studies reporting prevalence and clinical characteristics/outcomes of APA. Eight studies were analyzed for prevalence. Six studies reporting histopathological details were analyzed in depth. RESULTS: Of the 7105 included patients, 373 (5.2%) met criteria for APA (prevalence range: 3%-15%). Only 2 of 8 studies utilized identical grading criteria, demonstrating a lack of standardized application. Most APAs (84%) were macroadenomas, with 52% invasive on magnetic resonance imaging. Nonfunctional PAs were most common (37%), followed by prolactinomas (23%) and Growth Hormone adenomas (21%). Recurrence/progression occurred in 21% of APA patients (follow-up range 37-75 mo). Only 2 of 8 studies reported an association between APA diagnosis and recurrence/progression. CONCLUSION: Based on diagnostic variability and lack of association with clinical outcomes, refinement of criteria for APA was necessary. The WHO update eliminates the ambiguity in APA diagnosis in favor of criteria that emphasize clinical behavior (invasion, recurrence, and resistance to treatment) and molecular markers. Our review supports abandonment of the previous APA designation due to limited prognostic utility.