Cerebral cavernous malformations do not fall in the spectrum of PIK3CA-related overgrowth.

Somatic gain-of-function (GOF) mutations in phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), the catalytic subunit of phosphoinositide 3-kinase (PI3K), have been recently discovered in cerebral cavernous malformations (CCMs), raising the possibility that the activation of PI3K pathways is a possible universal regulator of vascular morphogenesis. However, there have been contradicting data presented among various groups and studies. To enhance the current understanding of vascular anomalies, it is essential to explore this possible relationship between altered PI3K signalling pathways and its influence on the pathogenesis of CCMs. GOF PIK3CA-mutants have been linked to overgrowth syndromes, allowing this group of disorders, resulting from somatic activating mutations in PIK3CA, to be collectively named as PIK3CA-related overgrowth spectrum disorders. This paper reviews and attempts to conceptualise the relationships and differences among clinical presentations, genotypic and phenotypic correlations and possible coexistence of PIK3CA and CCM mutations/phenotypes in CCM lesions. Finally, we present a model reflecting our hypothetical understanding of CCM pathogenesis based on a systematic review and conceptualisation of data obtained from other studies.

Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord.

Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

Timing of surgical treatment for idiopathic normal pressure hydrocephalus: association between treatment delay and reduced short-term benefit.

OBJECTIVE A growing body of evidence suggests that longer durations of preoperative symptoms may correlate with worse postoperative outcomes following cerebrospinal fluid (CSF) diversion for treatment of idiopathic normal pressure hydrocephalus (iNPH). The aim of this study is to determine whether the duration of preoperative symptoms alters postoperative outcomes in patients treated for iNPH. METHODS The authors conducted a retrospective review of 393 cases of iNPH involving patients treated with ventriculoperitoneal (VP) shunting. The duration of symptoms prior to the operative intervention was recorded. The following outcome variables were assessed at baseline, 6 months postoperatively, and at last follow-up: gait performance, urinary continence, and cognition. RESULTS The patients' median age at shunt placement was 74 years. Increased symptom duration was significantly associated with worse gait outcomes (relative risk (RR) 1.055 per year of symptoms, p = 0.037), and an overall absence of improvement in any of the classic triad symptomology (RR 1.053 per year of symptoms, p = 0.033) at 6 months postoperatively. Additionally, there were trends toward significance for symptom duration increasing the risk of having no 6-month postoperative improvement in urinary incontinence (RR 1.049 per year of symptoms, p = 0.069) or cognitive symptoms (RR 1.051 per year of symptoms, p = 0.069). However, no statistically significant differences were noted in these outcomes at last follow-up (median 31 months). Age stratification by decade revealed that prolonging symptom duration was significantly associated with lower Mini-Mental Status Examination scores in patients aged 60-70 years, and lack of cognitive improvement in patients aged 70-80 years. CONCLUSIONS Patients with iNPH with longer duration of preoperative symptoms may not receive the same short-term benefits of surgical intervention as patients with shorter duration of preoperative symptoms. However, with longer follow-up, the patients generally reached the same end point. Therefore, when managing patients with iNPH, it may take longer to see the benefits of CSF shunting when patients present with a longer duration of preoperative symptoms.

Postradiation imaging changes in the CNS: how can we differentiate between treatment effect and disease progression?

A familiar challenge for neuroradiologists and neuro-oncologists is differentiating between radiation treatment effect and disease progression in the CNS. Both entities are characterized by an increase in contrast enhancement on MRI and present with similar clinical signs and symptoms that may occur either in close temporal proximity to the treatment or later in the disease course. When radiation-related imaging changes or clinical deterioration are mistaken for disease progression, patients may be subject to unnecessary surgery and/or a change from otherwise effective therapy. Similarly, when disease progression is mistaken for treatment effect, a potentially ineffective therapy may be continued in the face of progressive disease. Here we describe the three types of radiation injury to the brain based on the time to development of signs and symptoms--acute, subacute and late--and then review specific imaging changes after intensity-modulated radiation therapy, stereotactic radiosurgery and brachytherapy. We provide an overview of these phenomena in the treatment of a wide range of malignant and benign CNS illnesses. Finally, we review the published data regarding imaging techniques under investigation to address this well-known problem.

Imaging changes following stereotactic radiosurgery for metastatic intracranial tumors: differentiating pseudoprogression from tumor progression and its effect on clinical practice.

Stereotactic radiosurgery has become standard adjuvant treatment for patients with metastatic intracranial lesions. There has been a growing appreciation for benign imaging changes following radiation that are difficult to distinguish from true tumor progression. These imaging changes, termed pseudoprogression, carry significant implications for patient management. In this review, we discuss the current understanding of pseudoprogression in metastatic brain lesions, research to differentiate pseudoprogression from true progression, and clinical implications of pseudoprogression on treatment decisions.

Recommencement of anticoagulation in chronic subdural haematoma: a systematic review and meta-analysis.

OBJECTIVE: Chronic subdural haematoma (CSDH) is becoming an increasingly important neurosurgical condition, especially given the aging world population and the increasing use of anticoagulant and antiplatelet medication. Clinicians regularly confront the dilemma of whether or not to restart anticoagulant and antiplatelet medication after CSDH, yet there is little evidence to support the decision-making process. This systematic review and meta-analysis aims to address this specific question. METHODS: This systematic review and meta-analysis was conducted according to the PRISMA guidelines and has been registered with the PROSPERO international prospective register of systematic reviews (registration number CRD42012002509). Databases including MEDLINE, Cochrane, ISI Web of Knowledge, Embase and Google Scholar were searched for retrospective and prospective studies looking specifically at patients presenting with CSDH whilst on anticoagulant or antiplatelet medication which had data on subsequent recurrence and thromboembolic events. RESULTS: Three relevant studies were found, totalling to 64 patients. In those restarted on anticoagulation, 11.1% experienced recurrences and 2.2% experienced thromboembolic events. In the control group that was not restarted on anticoagulation, 22.2% experienced recurrences and no patient experienced thromboembolic events. All recurrences and thromboembolic events occurred within the first 4 weeks of the initial surgical evacuation. CONCLUSIONS: The review seems to paradoxically suggest a lower bleeding risk and a higher thromboembolism risk when anticoagulation is restarted, although few concrete conclusions can be drawn from a pool of 64 patients. The decision on whether or not to restart anticoagulation in patients who present with CSDH whilst on anticoagulation has little empirical evidence to support a decision either way; more data are required to allow clinicians to make informed decisions about whether or not to restart anticoagulation, and if so, which drug, at what time-point and at what dose/therapeutic target.

Letter to Our Colleagues Family Practitioners, Geriatricians, and Radiologists to Increase Awareness Regarding Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) affects elderly individuals and is characterized by a progressive deterioration of gait, urinary continence, and cognition. In most cases, it is reversible with treatment. INPH is not uncommonly an unrecognized cause of dementia. We wish to raise awareness of iNPH among primary care providers who are seeing these patients first. METHODS: We reviewed the current epidemiological data regarding iNPH as well as epidemiological data regarding Alzheimer disease. We searched for the most sensitive radiological screening test for iNPH. RESULTS: Alzheimer disease comprises 60%-70% of all dementia cases, in 2023 is affecting 6.7 million Americans, about 10.7% of people 65 and older. Epidemiological data from the Scandinavian countries confirmed that 3.7% of people older than 65 have iNPH. Surgical studies confirmed the presence of early Alzheimer's pathology in about 25% of operated patients with iNPH. Useful radiological findings of iNPH include an Evans Index greater than 0.30, and a disproportionally enlarged subarachnoid space hydrocephalus (DESH). However, the callosal angle is thought to represent the best tool to discriminate iNPH from its mimics. CONCLUSIONS: According to the available epidemiological data iNPH is underdiagnosed. We strongly encourage the primary care physicians and geriatricians to ask the radiologist to measure the callosal angle on the initial brain computed tomography (or magnetic resonance) image. If the callosal angle is ≤71°, it is appropriate to refer the patient to neurosurgery for further diagnostic work-up.

Visual and neurological outcomes following endovascular stenting for pseudotumor cerebri associated with transverse sinus stenosis.

BACKGROUND: Pseudotumor cerebri (PTC) is characterized by raised intracranial pressure (ICP) without an identifiable mass, evidence of hydrocephalus, or abnormal cerebrospinal fluid content. In the past, most cases of PTC appeared to have no identifiable etiology, and thus, they were classified as "idiopathic intracranial hypertension" (IIH). Recently, however, a subset of patients with presumed IIH has been found to have evidence of cerebral dural sinus stenoses, particularly involving one or both transverse sinuses (TS). The belief that the stenoses are the cause, rather than an effect of the increased ICP, has led investigators to recommend stenting of the stenosed sinus for the treatment of the condition. We describe detailed visual and neurological outcomes after stenting for PTC associated with hemodynamically significant dural sinus stenosis. METHODS: All patients with PTC had initial neurological, neuro-ophthalmological, and imaging assessments. Regardless of the findings, all were treated with medical therapy. If medical therapy failed and TS stenosis was detected on contrast-enhanced magnetic resonance or computed tomographic venography, catheter cerebral angiography with venous manometry was performed. If a mean pressure gradient (MPG) of 4 mm Hg or greater was present, unilateral transverse sinus stenting was performed. RESULTS: Twelve patients with PTC and TS stenosis associated with an MPG of >4 mm Hg who failed medical therapy were identified. TS stenting significantly decreased the pressure gradient in all cases. Unilateral stenting was sufficient to reduce pressure gradients even when the stenosis was bilateral. At a mean follow-up of 16 months (range, 9-36 months), tinnitus had improved in all patients, and 10 of 12 patients had improvement in visual function. Seven patients had significant improvement in headaches. CONCLUSION: In this small series of patients with PTC associated with TS stenosis, endovascular stent placement was generally effective in treating visual dysfunction and tinnitus, although not headaches. The optimum gradient and vascular characteristics amenable for selection of patients for stenting needs further research.

Readmissions in patients with cerebral cavernous malformations: a national readmission database study.

BACKGROUND: Cerebral cavernous malformations (CCMs) are microvascular CNS lesions prone to hemorrhage leading to neurological sequela such as stroke and seizure. A subset of CCM patients have aggressive disease leading to multiple bleeding events, likely resulting multiple hospitalizations. Hospital admission rates are an important metric that has direct financial impact on hospitals and an indicator of overall disease burden. Furthermore, analysis of hospital readmissions can lead to early identification of high-risk patients and provides insight into the pathogenesis of CCM lesions. The purpose of this study is to identify high risk CCM patients with increased all cause readmission and comorbidities associated with increased readmissions. METHODS: All US hospital admissions due to CCMs were searched using the 2017 National Readmission Database (NRD). Patients with readmissions within 30 days of discharge from index hospitalization were identified and analyzed, relative to the remaining population. RESULTS: Among all patients hospitalized for CCM, 14.9% (13.7-16.2%) required all cause readmission within 30 days. Multivariate logistical regression analysis showed that substance abuse (P=0.003), diabetes (P=0.018), gastrointestinal bleed (P=0.002), renal failure (P=0.027), and coronary artery disease (P=0.010) were predictive of all cause readmissions, while age group 65-74 (P=0.042), private insurance (P<0.001), and treatment at a metropolitan teaching institution (P=0.039) were protective. Approximately half of all readmissions are caused by neurological (33.9%) and infectious (14.6%) etiologies. The 30-day lesion bleeding rate after index hospitalization is 0.8% (0.5-1.2%). CONCLUSIONS: All identified comorbidities associated with increased risks of readmission contribute to vascular stress, suggesting its role in lesion pathogenesis. This is the first and only study to analyze readmission metrics for CCMs in order to identify high risk patient factors to date.

Management of hemorrhage from cavernous malformations.

Cavernous Malformations (CMs) are immature vessels consisting of endothelium-lined sinusoids. Often diagnosed incidentally, they remain clinically silent in the vast majority of patients. Their natural history is now largely believed to follow a benign course that should be conservatively managed in the majority of cases. The exception is the treatment of deep lesions. Here there is not a consensus but the general inclination is towards radiosurgical treatment of inaccessible lesions. However, the results of radiosurgical or gross surgical resection have not been shown to be significantly better than many patients who were managed conservatively. In view of this, an understanding of the natural history of CM and the various outcomes from surgery, radiosurgery and conservative management are essential to define the goals for patients and to individualize treatment strategy.

Preliminary Validation of FoRCaSco: A New Grading System for Cerebral and Cerebellar Cavernomas.

OBJECTIVE: Surgical indications for cerebral cavernous malformations (CCMs) remain significantly center- and surgeon-dependent; available grading systems are potentially limited, as they do not include epileptologic and radiologic data. Several experienced authors proposed a new grading system for CCM and the first group of patients capable of providing its statistical validation was analyzed. METHODS: A retrospective series of 289 CCMs diagnosed between 2008 and 2021 was collected in a shared anonymous database among 9 centers. The new grading system ranges from -1 to 10. For each patient with cortical and cerebellar cavernous malformations the grading system was applied, and a retrospective outcome analysis was performed. We proposed a score of 4 as a cutoff for surgical indication. RESULTS: Operated patients with a score ≥4 were grouped with non-operated patients with a score <4, as they constituted the group that received correct treatment according to the new grading system. Patients with a score ≥4, who underwent surgery and had an improved outcome, were compared to patients with a score ≥4 who were not operated (P = 0.04), and to patients with a score <4 who underwent surgery (P < 0.001). CONCLUSIONS: This preliminary statistical analysis demonstrated that this new grading would be applicable in surgical reality. The cutoff score of 4 correctly separated the patients who could benefit from surgical intervention from those who would not. The outcome analysis showed that the treated patients in whom the grading system has been correctly applied have a better outcome than those in whom the grading system has not been applied.

Impact of international research fellows in neurosurgery: results from a single academic center.

OBJECTIVE: International research fellows have been historically involved in academic neurosurgery in the United States (US). To date, the contribution of international research fellows has been underreported. Herein, the authors aimed to quantify the academic output of international research fellows in the Department of Neurosurgery at The Johns Hopkins University School of Medicine. METHODS: Research fellows with Doctor of Medicine (MD), Doctor of Philosophy (PhD), or MD/PhD degrees from a non-US institution who worked in the Hopkins Department of Neurosurgery for at least 6 months over the past decade (2010-2020) were included in this study. Publications produced during fellowship, number of citations, and journal impact factors (IFs) were analyzed using ANOVA. A survey was sent to collect information on personal background, demographics, and academic activities. RESULTS: Sixty-four international research fellows were included, with 42 (65.6%) having MD degrees, 17 (26.6%) having PhD degrees, and 5 (7.8%) having MD/PhD degrees. During an average 27.9 months of fellowship, 460 publications were produced in 136 unique journals, with 8628 citations and a cumulative journal IF of 1665.73. There was no significant difference in total number of publications, first-author publications, and total citations per person among the different degree holders. Persons holding MD/PhDs had a higher number of citations per publication per person (p = 0.027), whereas those with MDs had higher total IFs per person (p = 0.048). Among the 43 (67.2%) survey responders, 34 (79.1%) had nonimmigrant visas at the start of the fellowship, 16 (37.2%) were self-paid or funded by their country of origin, and 35 (81.4%) had mentored at least one US medical student, nonmedical graduate student, or undergraduate student. CONCLUSIONS: International research fellows at the authors' institution have contributed significantly to academic neurosurgery. Although they have faced major challenges like maintaining nonimmigrant visas, negotiating cultural/language differences, and managing self-sustainability, their scientific productivity has been substantial. Additionally, the majority of fellows have provided reciprocal mentorship to US students.

Ccm1 regulates microvascular morphogenesis during angiogenesis.

Cerebral cavernous malformations (CCMs) are characterized by abnormally dilated intracranial capillaries that have a propensity to bleed. The development of some CCMs in humans has been attributed to mutations in CCM1 and CCM2 genes. In animal models, major cardiovascular defects caused by both gene mutations have been observed. However, the effects of the loss of Ccm function on the microvasculature in animal models are less defined. Using high-resolution imaging in vivo, we demonstrated that the loss of Ccm1 in zebrafish embryos leads to failed microvascular lumenization during angiogenesis due to impaired intraendothelial vacuole formation and fusion. No developmental changes during vasculogenesis and the initial stage of angiogenesis were observed, being in contrast to prior reports. In vivo zebrafish studies were further substantiated by in vitro findings in human endothelial cells that elucidated the biochemical pathways of CCM1 deficiency. We found that CCM1 regulates angiogenic microvascular lumen formation through Rac1 small GTPase. In summary, Ccm1 has been identified as a key angiogenic modulator in microvascular tubulogenesis. Additionally, the microvascular pathology observed in developing Ccm1 mutant zebrafish embryos mirrors that seen in human CCM lesions, suggesting that zebrafish might provide a superior animal model to study the pathogenesis of human CCM.

Genome-wide linkage scan maps ETINPH gene to chromosome 19q12-13.31.

OBJECTIVE: Essential tremor (ET), one of the most common neurological disorders, comprises uncontrollable tremor, usually in the upper extremities. Idiopathic normal pressure hydrocephalus (iNPH) features ventricular enlargement in the absence of elevated intracranial pressure; its three cardinal symptoms are gait impairment, incontinence, and dementia. iNPH is among the most common medical problems in the older population. To date, the genetic etiologies of ET and iNPH remain largely elusive. METHODS: We previously identified a large kindred in which the affected members developed ET in adolescence or young adulthood and iNPH when elderly, in that case called ETINPH. Employing two different genotyping microarrays and two- or multipoint linkage analysis strategies, genome-wide linkage scans were performed. RESULTS: We mapped the ETINPH locus to chromosome 19q12-13.31. Fine-mapping in this region revealed a maximum two-point lod score of 2.8 at rs2023865 and a maximum multipoint lod score of 17.9 at rs9304878. By haplotype construction, a (conservatively) approximately 17-cM critical region from SNP rs11084582 to SNP rs7258420 was defined. This region contains several neuronal genes that constitute tantalizing etiological candidates for ETINPH. CONCLUSION: The importance of uncovering the genetic etiology of this disorder is irrefutable, as such a discovery could offer valuable insights into ET, iNPH, and related neurological conditions.

Achieving and Maintaining Safety in Healthcare Requires Unwavering Institutional and Individual Commitments.

In 2000, "To Err Is Human" brought to light the fact that the estimated number of people dying from medical errors occurring in hospitals exceeded those that die from motor vehicle accidents (MVAs), breast cancer, or acquired immunodeficiency syndrome (AIDS) - three causes receiving far more public attention. The report prompted the gradual adoption of safety processes developed in the nuclear and aviation industries. However, sophisticated engineering solutions to operations are not enough. High and low mortality hospitals have similar processes and procedures, but low-mortality hospitals are more proficient at recognizing and managing serious complications as they unfold. This ability to rescue a deteriorating situation (resilience) reflects a healthier safety culture. Organizations move within the safety space in the direction of either more or less resilience depending on the fluctuation of their safety culture. Improving resilience requires transforming learned safety practices into a "habit" in conjunction with accepting accountability. Personal accountability means commitment to safe practices along with effective and transparent reporting of near misses/close calls and adverse events (AEs). Institutional accountability means putting safety first by ensuring the availability of appropriate resources, role leadership modeling, and effective management of sentinel events (SEs) to reduce harm occurrence and re-occurrence. This requires a more robust root cause analysis (RCA) process to guarantee that action plans produce strong and effective corrective measures. Synergistic coaching interventions include instilling the awareness that failure can and will happen, mapping team talents, and assessing gaps. These interventions will optimize group expertise, reaffirming the concept of institutional and personal accountability. The unending performance of drills will sustain the group resilience under both expected and unexpected conditions. Given the strong correlation between practice environment and outcomes, sustained improvement of the safety climate will produce more robust safety behaviors and ultimately better outcomes.

An international call for a new grading system for cerebral and cerebellar cavernomas.

Surgical indications for cerebral cavernous malformations remain significantly center- and surgeon-dependent. Available grading systems are potentially limited, as they do not include epileptological and radiological data. A novel grading system is proposed for supratentorial and cerebellar cavernomas: it considers neuroradiological features (bleeding, increase in size), neurological status (focal deficits and seizures), location of the lesion and age of the patient. The score ranges from -1 to 10; furthermore, surgery should be considered when a score of 4 or higher is present. Based on neuroradiological characteristics, 0 points are assigned if the CCM is stable in size at different neuroradiological controls, 1 point if there is an increase in volume during follow-up, 2 points if intra- or extra-lesional bleeding <1 cm is present and 3 points if the CCM produced a hematoma >1 cm. Regarding focal neurological deficits, 0 points are assigned if absent and 2 points if present. For seizures, 0 points are assigned if absent, 1 point if present, but controlled by medications, and 2 points if drug resistant. We considered the site of the CCM, and in case of deep-seated lesions in a critical area (basal ganglia, thalamus) 1 point (-1) is subtracted, while for subcortical or deep cerebellar lesions 0 points are assigned, for CCMs in a cortical critical area 1 point is assigned and in case of lesions in cortical not in critical area or superficial cerebellar area, 2 points are assigned. As far as age is concerned, 0 points are assigned for patients older than 50 years and 1 point for patients younger than 50. In conclusion, a novel grading for surgical decision making in cerebral cavernomas, based on the experience of selected neurosurgeons, basic scientists, and patients, is suggested with the aim of further improving and standardizing the treatment of CCMs. The aim of this paper was also to call for both retrospective and prospective multicenter studies with the aim of testing the efficacy of the grading system in different centers.

Spinal epidural abscess: current diagnosis and management.

Spinal epidural abscess (SEA) is an uncommon condition that warrants urgent diagnosis and treatment, because early pharmacotherapy significantly improves prognosis and prompt surgical decompression is often necessary to prevent or minimize neurologic complications. Increased awareness is critical; any of the characteristic clinical findings, especially in the presence of risk factors and elevated inflammatory markers, should lead to heightened suspicion for SEAs and its consideration on differential diagnosis, even in the absence of neurologic deficits. A multidisciplinary approach is essential for successful management of SEAs; along with infectious disease specialists and neurosurgeons/orthopedic spine surgeons, primary care, emergency medicine, and internal medicine clinicians are more likely to see patients with SEAs at earlier stages and play a pivotal role in early diagnosis and treatment. A combination of targeted antibiotic therapy and prompt surgical decompression is recommended in most cases, although medical management alone can be effective in select patients under close monitoring.

Stereotactic radiosurgery for spine tumors: review of current literature.

Stereotactic radiosurgery (SR) is increasingly utilized for the treatment of intracranial and extracranial pathology. It is considered an important adjuvant to surgery, chemotherapy or fractionated radiotherapy, and the role of SR as a primary treatment modality continues to be explored. Although SR for spinal lesions is in its infancy, there is a growing body of literature supporting its efficacy. The purpose of this review is to summarize the pertinent literature regarding the use of SR for lesions of the spine and spinal cord. Particular emphasis will be placed on large clinical series of both primary and secondary spine tumors.

Treatment of pituitary adenomas using radiosurgery and radiotherapy: a single center experience and review of literature.

Fractionated radiotherapy (FRT) and gamma knife stereotactic radiosurgery (GKSRS) are used as adjuvant therapies to surgical resection for functional and non-functional pituitary adenomas, although their optimum role in the treatment algorithm, as well as long-term safety and efficacy, still awaits further study. We report a single center experience with 33 patients with non-functional (16 patients), ACTH- (five patients), GH- (four patients), or prolactin-secreting (eight patients) tumors treated with FRT or SRS. The median tumor diameter was 1.9 cm, and the median follow-up was 36 months. For GKSRS, the median dosage was 16 Gy for non-functional adenomas and 23 Gy for hormone-secreting tumors. The median total dose for FRT was 50.4 Gy over 28 fractions (median). Two patients (6%) demonstrated radiographic evidence of tumor progression, three patients (9%) demonstrated radiation-induced visual field deficits on neuro-ophthalmic evaluation, and two patients (6%) suffered from radiation-induced hypopituitarism. Biochemical control, defined as normalized hormone values in the absence of medical therapy, was achieved in five out of eight prolactinoma patients and two out of five patients with Cushing's disease, but none of the four patients with acromegaly. These results are presented with a review of the relevant literature on the differential characteristics of FRT versus SRS in the treatment of functional and non-functional pituitary adenomas and validate postoperative irradiation as a potentially safe and effective means for tumor control.