[Postoperative risk of bleeding after removal of third molars in healthy patients - a prospective observational clinical study]. / Nabloedingsrisico na verwijdering derde molaar bij gezonde patiënten; een prospectief observationeel klinisch onderzoek.

Removal of third molars in healthy patients is considered a procedure with a low risk of bleeding. However, exactly how low the incidence of postoperative bleeding is remains unclear due to the heterogeneity of available studies. To determine the exact postoperative risk of bleeding after the removal of third molars in healthy patients, a prospective observational multicentre study was conducted. A total of 1,035 patients with complete follow-up was included. Of these, 329 patients reported subsequent bleeding, but did not consult their attending physician. A total of 15 patients visited the hospital, 8 of whom required minimally invasive (re)treatment. No hospitalizations were necessary. There was a large difference between the incidence of postoperative bleeding reported by patients and postoperative bleeding requiring clinical examination and/or treatment. To reduce this difference in future, patients should be given detailed information about what degree of postoperative bleeding is considered normal after removal of a third molar.

Diagnostics and treatment delay in primary central nervous system lymphoma: What the neurosurgeon should know.

PURPOSE: The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL. METHODS: We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery. RESULTS: Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics. CONCLUSION: Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs.

Statistical groupings of mental and social health measurements correlate with musculoskeletal capability - A cross sectional study.

OBJECTIVE: A better understanding of the degree to which social health factors contribute uniquely to statistical clusters associated with variation in levels of capability might inform targeted whole person care strategies for more comprehensive management of musculoskeletal health. Therefore, we asked: (1) What are the statistical groupings of social and mental health measurements in patients seeking specialty care for musculoskeletal conditions? (2) Do identified psychosocial groupings correspond with different mean magnitudes of incapability accounting for demographic and clinical factors? METHODS: We included 158 patients seeking musculoskeletal specialty care and collected measures of magnitude of incapability, unhelpful thoughts and distress regarding symptoms, symptoms of depression, symptoms of anxiety, and social health. A k-means clustering algorithm was fit to the data and a linear regression model compared mean PROMIS-PF CAT scores for grouping. RESULTS: A quantitative social health measure contributed to 4 statistical clusters as follows: 1) relatively low levels of all mental health measures and high social health; 2) greater unhelpful thoughts and distress regarding symptoms, average symptoms of general anxiety and depression, and average social health; 3) higher levels of all mental health measures and severely compromised social health; and 4) severely compromised mental health and lower social health. Magnitude of incapability was significantly greater for groups with worse mental and social health. CONCLUSION: The finding of a relatively independent association of social and mental health factors with greater incapability supports the importance of introducing comprehensive health strategies in musculoskeletal specialty care. Strategies may include mindset training and case management of social unmet needs. LEVEL OF EVIDENCE: Level III; Cross-sectional study.

Permanent stoma rate and long-term stoma complications in laparoscopic, robot-assisted, and transanal total mesorectal excisions: a retrospective cohort study.

BACKGROUND: The surgical resection of rectal carcinoma is associated with a high risk of permanent stoma rate. Primary anastomosis rate is suggested to be higher in robot-assisted and transanal total mesorectal excision, but permanent stoma rate is unknown. METHODS: Patients undergoing total mesorectal excision for MRI-defined rectal cancer between 2015 and 2017 in 11 centers highly experienced in laparoscopic, robot-assisted or transanal total mesorectal excision were included in this retrospective study. Permanent stoma rate, stoma-related complications, readmissions, and reoperations were registered. A multivariable regression analysis was performed for permanent stoma rate, stoma-related complications, and stoma-related reoperations. RESULTS: In total, 1198 patients were included. Permanent stoma rate after low anterior resection (with anastomosis or with an end colostomy) was 40.1% in patients undergoing laparoscopic surgery, 21.3% in patients undergoing robot-assisted surgery, and 25.6% in patients undergoing transanal surgery (P < 0.001). Permanent stoma rate after low anterior resection with an anastomosis was 17.3%, 11.8%, and 15.1%, respectively. The robot-assisted and transanal techniques were independently associated with a reduction in permanent stoma rate in patients who underwent a low anterior resection (with anastomosis or with an end colostomy) (OR 0.39 [95% CI 0.25, 0.59] and OR 0.35 [95% CI 0.22, 0.55]), while this was not seen in patients who underwent a restorative low anterior resection. 45.4% of the patients who had a stoma experienced stoma-related complications, 4.0% were at least once readmitted, and 8.9% underwent at least one reoperation. CONCLUSIONS: The robot-assisted and transanal techniques are associated with a lower permanent stoma rate in patients who underwent a low anterior resection.

SAFESTEREO: phase II randomized trial to compare stereotactic radiosurgery with fractionated stereotactic radiosurgery for brain metastases.

BACKGROUND: Stereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases. METHODS: Patients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15-24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life. DISCUSSION: Currently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure. TRIAL REGISTRATION: ClincalTrials.gov, trial registration number: NCT05346367 , trial registration date: 26 April 2022.

Visualization, navigation, augmentation. The ever-changing perspective of the neurosurgeon.

Introduction: The evolution of neurosurgery coincides with the evolution of visualization and navigation. Augmented reality technologies, with their ability to bring digital information into the real environment, have the potential to provide a new, revolutionary perspective to the neurosurgeon. Research question: To provide an overview on the historical and technical aspects of visualization and navigation in neurosurgery, and to provide a systematic review on augmented reality (AR) applications in neurosurgery. Material and methods: We provided an overview on the main historical milestones and technical features of visualization and navigation tools in neurosurgery. We systematically searched PubMed and Scopus databases for AR applications in neurosurgery and specifically discussed their relationship with current visualization and navigation systems, as well as main limitations. Results: The evolution of visualization in neurosurgery is embodied by four magnification systems: surgical loupes, endoscope, surgical microscope and more recently the exoscope, each presenting independent features in terms of magnification capabilities, eye-hand coordination and the possibility to implement additional functions. In regard to navigation, two independent systems have been developed: the frame-based and the frame-less systems. The most frequent application setting for AR is brain surgery (71.6%), specifically neuro-oncology (36.2%) and microscope-based (29.2%), even though in the majority of cases AR applications presented their own visualization supports (66%). Discussion and conclusions: The evolution of visualization and navigation in neurosurgery allowed for the development of more precise instruments; the development and clinical validation of AR applications, have the potential to be the next breakthrough, making surgeries safer, as well as improving surgical experience and reducing costs.

Ethical implications of visual neuroprostheses-a systematic review.

Objective. The aim of this review was to systematically identify the ethical implications of visual neuroprostheses.Approach. A systematic search was performed in both PubMed and Embase using a search string that combined synonyms for visual neuroprostheses, brain-computer interfaces (BCIs), cochlear implants (CIs), and ethics. We chose to include literature on BCIs and CIs, because of their ethically relavant similarities and functional parallels with visual neuroprostheses.Main results. We included 84 articles in total. Six focused specifically on visual prostheses. The other articles focused more broadly on neurotechnologies, on BCIs or CIs. We identified 169 ethical implications that have been categorized under seven main themes: (a) benefits for health and well-being; (b) harm and risk; (c) autonomy; (d) societal effects; (e) clinical research; (f) regulation and governance; and (g) involvement of experts, patients and the public.Significance. The development and clinical use of visual neuroprostheses is accompanied by ethical issues that should be considered early in the technological development process. Though there is ample literature on the ethical implications of other types of neuroprostheses, such as motor neuroprostheses and CIs, there is a significant gap in the literature regarding the ethical implications of visual neuroprostheses. Our findings can serve as a starting point for further research and normative analysis.

A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

Age, pathology and CA-125 are prognostic factors for survival in patients with brain metastases from gynaecological tumours.

BACKGROUND AND PURPOSE: Brain metastases originating from gynaecological tumours are a rare phenomenon, but have an increasing incidence due to better targeted therapies. This study aimed to identify factors that predict survival in these patients, which can be used in creating a robust prognostic tool for shared decision making. MATERIALS AND METHODS: We identified a consecutive cohort of 73 patients treated for gynaecological brain metastases in two tertiary institutions. Baseline demographics, pathology and serum CA-125 were included in a multivariable Cox proportional hazards model. RESULTS: Median overall survival in our cohort was 14.4 months, with a one-year survival of 56.4% and a two-year survival of 39.1%. Thirty-eight patients (52.1%) had ovarian carcinoma as the primary malignancy. The following factors were significantly associated with survival: age (HR 1.05 per year), CA-125 (HR 1.02 par 50 U/ml), and uterine and vulvar primary tumours (when compared to ovarian carcinoma, with HRs 3.07 and 8.70). A post-hoc analysis with primary tumour site reclassified into ovary versus non-ovary showed a HR of 0.50 for ovarian primary tumour type. CONCLUSION: We have found that age, pathology and CA-125 are prognostic factors for survival in patients with brain metastases from gynaecological tumours. Our findings may provide a foundation for future development of prediction models, for the benefit of both patients and physicians.

[The surgical learning curve]. / De chirurgische leercurve.

Surgical perfection takes years of training and a learning curve to optimize outcomes. This creates an ethical dilemma: although healthcare systems benefit from training new surgeons, the learning curve may cause suboptimal outcomes for the first patients a resident operates on. Can collective interest for the betterment of healthcare be combined with the wellbeing of the individual patient? We argue that this is possible under controlled circumstances. Residency programmes can optimize the learning curve of the trainee by active and extensive supervision: the 'See one, do one' mentality is outdated, even in relatively simple procedures. Residents can improve their skills by using hands-on training on animals or cadavers, or by re-watching their own procedures. It is possible that despite all preventative measures, the effect of the learning curve on surgical outcomes is inevitable and necessary where new surgeons are trained within regular healthcare systems. Ultimately, practice makes perfect.

Depression and survival of glioma patients: A systematic review and meta-analysis.

INTRODUCTION: There is currently a lack of a well-formed consensus regarding the effects of depression on the survival of glioma patients. A more thorough understanding of such effects may better highlight the importance of recognizing depressive symptoms in this patient population and guide treatment plans in the future. OBJECTIVE: The aim of this meta-analysis was to study the effect of depression on glioma patients' survival. METHODS: A meta-analysis was conducted according to the PRISMA guidelines. PubMed, Embase, and Cochrane databases were searched for studies that reported depression and survival among glioma patients through 11/06/2016. Both random-effects (RE) and fixed-effect (FE) models were used to compare survival outcomes in glioma patients with and without depression. RESULTS: Out of 619 identified articles, six were selected for the meta-analysis. Using RE model, the various measures for survival outcomes displayed worsened outcomes for both high and low-grade glioma patients with depression compared to those without depression. For binary survival outcomes, the overall pooled risk ratio for survival was 0.70 (95% CI: 0.47, 1.04; 6 studies; I2 = 54.9%, P-heterogeneity = 0.05) for high grade gliomas (HGG) and 0.28 (95% CI: 0.04, 1.78; I2 = 0%, P-heterogeneity = 1.00; one study) for low grade gliomas (LGG) was. A sub-group analysis in the HGG group by depression timing (pre- versus post-operative) revealed no differences between depression and survival outcomes (P-interaction = 0.47). For continuous survival outcomes, no statistically significant difference was found among the high and low-grade glioma groups (P-interaction = 0.31). The standardized mean difference (SMD) in survival outcomes was -0.56 months (95%CI: -1.13, 0.02; 4 studies, I2 = 89.4%, P-heterogeneity < 0.01) for HGG and -1.69 months (95%CI: -3.26, -0.13; one study; I2 = 0%, P-heterogeneity = 1.00) for LGG. In patients with HGG, the pooled HR of death also showed a borderline significant increased risk of death among depressive patients (HR 1.42, 95% CI: 1.00, 2.01). Results using the FE model were not materially different. CONCLUSIONS: Depression was associated with significantly worsened survival regardless of time of diagnosis, especially among patients with high-grade glioma.

Clinical challenges of glioma and pregnancy: a systematic review.

INTRODUCTION: This review aims to summarize challenges in clinical management of concomitant gliomas and pregnancy and provides suggestions for this management based on current literature. METHODS: PubMed and Embase databases were systematically searched for studies on glioma and pregnancy. Observational studies and articles describing expert opinions on clinical management were included. The strength of evidence was categorized as arguments from observational studies, consensus in expert opinions, or single expert opinions. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS). RESULTS: 27 studies were selected, including 316 patients with newly diagnosed (n = 202) and known (n = 114) gliomas during pregnancy. The median sample size was 6 (range 1-65, interquartile range 1-9). Few recommendations originated from observational studies; the remaining arguments originated from consensus in expert opinions. CONCLUSION: Findings from observational studies of adequate quality include (1) There is no known effect of pregnancy on survival in low-grade glioma patients; (2) Pregnancy can provoke clinical deterioration and tumor growth on MRI; (3) In stable women at term, there is no benefit of cesarean section over vaginal delivery, with respect to adverse events in mother or child. Unanswered questions include when pregnancy should be discouraged, what best monitoring schedule is for both mother and fetus, and if and how chemo- and radiation therapy can be safely administered during pregnancy. A multicenter individual patient level meta-analysis collecting granular information on clinical management and related outcomes is needed to provide scientific evidence for clinical decision-making in pregnant glioma patients.

A prognostic role for Low tri-iodothyronine syndrome in acute stroke patients: A systematic review and meta-analysis.

BACKGROUND: Low triiodothyronine (T3) syndrome could be a powerful prognostic factor for acute stroke; yet, a prognostic role for low T3 has not been given enough importance in stroke management. This meta-analysis aimed to evaluate whether low T3 among acute stroke patients could be used as a prognostic biomarker for stroke severity, functional outcome, and mortality. METHODS: Studies that investigated low T3 prognostic roles in acute stroke patients were sought from PubMed/Medline, Embase, and Cochrane databases through 11/23/2016. Pooled estimates of baseline stroke severity, mortality, and functional outcomes were assessed from fixed-effect (FE) and random-effects (RE) models. RESULTS: Eighteen studies met the inclusion criteria. Six studies (1,203 patients) provided data for low-T3 and normal-T3 patients and were meta-analyzed. Using the FE model, pooled results revealed low-T3 patients exhibited a significantly higher stroke severity, as assessed by the National Institutes of Health Stroke Scale (NIHSS) score at admission (mean difference = 3.18; 95%CI = 2.74, 3.63; I2 = 61.9%), had 57% higher risk of developing poor functional outcome (RR = 1.57; 95%CI = 1.33,1.8), and had 83% higher odds of mortality (Peto-OR = 1.83; 95%CI = 1.21, 1.99) compared to normal-T3 patients. In a univariate meta-regression analysis, the low-T3 and stroke severity association was reduced in studies with higher smokers% (slope = -0.11; P = 0.02), higher hypertension% (slope = -0.11; P = 0.047), older age (slope = -0.54; P = 0.02), or longer follow-up (slope = -0/17, P < 0.01). RE models yielded similar results. No significant publication bias was observed for either outcome using Begg's and Egger's tests. CONCLUSIONS: Low-T3 syndrome in acute stroke patients is an effective prognostic factor for predicting greater baseline stroke severity, poorer functional outcome, and higher overall mortality risk.

The glutathione transferase Mu null genotype leads to lower 6-MMPR levels in patients treated with azathioprine but not with mercaptopurine.

The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 108 RBCs; P<0.01). In patients on MP (control group) 6-MMPR levels were comparable (6195 (1551-10712) versus 6544 (1717-11600) pmol/8 × 108 RBCs; P=0.84). The 6-TGN levels were not affected by the GSTM1 genotype. The presence of genetic variants in GSTA1 and GSTA2 was not related to the 6-MMPR and 6-TGN levels.

Risk factors for thiopurine-induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype.

BACKGROUND: Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases. AIM: To identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. METHODS: Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial. For this analysis, patients without a variant in TPMT (*2, *3A or*3C) were included. Uni- and multivariate Cox-proportional hazard models were used to identify risk factors for leucopenia and infections. Leucopenia was defined as a white blood cell (WBC) count <3.0 × 109 /L and infections were classified according to the Common Terminology Criteria for Adverse Events. RESULTS: Sixty hundred and ninety-five patients (90.6%) included in the TOPIC-trial had no variant in TPMT, of which 45 (6.5%) developed leucopenia. Median time to leucopenia was 56 (29-112) days. Multivariate analysis showed that use of mercaptopurine compared to azathioprine was associated with leucopenia (hazard ratio [HR] 2.61 [95% CIs, 1.39-4.88; P < .01]) and a higher baseline WBC count was protective (HR 0.80 [95% CIs, 0.71-0.89; P < .01]). Risk factors for infections were older age (per 10 year; HR 2.07 [95% CIs, 1.18-3.63; P = .01]) and concomitant use of biologic drugs (HR 2.15 [95% CIs, 1.14-4.07; P = .02]). CONCLUSIONS: Low baseline WBC count and mercaptopurine, due to a relatively higher dose, were risk factors for thiopurine-induced leucopenia in patients without a TPMT variant.

Innovation in neurosurgery: less than IDEAL? A systematic review.

BACKGROUND: Surgical innovation is different from the introduction of novel pharmaceuticals. To help address this, in 2009 the IDEAL Collaboration (Idea, Development, Exploration, Assessment, Long-term follow-up) introduced the five-stage framework for surgical innovation. To evaluate the framework feasibility for novel neurosurgical procedure introduction, two innovative surgical procedures were examined: the endoscopic endonasal approach for skull base meningiomas (EEMS) and the WovenEndobridge (WEB device) for endovascular treatment of intracranial aneurysms. METHODS: The published literature on EEMS and WEB devices was systematically reviewed. Identified studies were classified according to the IDEAL framework stage. Next, studies were evaluated for possible categorization according to the IDEAL framework. RESULTS: Five hundred seventy-six papers describing EEMS were identified of which 26 papers were included. No prospective studies were identified, and no studies reported on ethical approval or patient informed consent for the innovative procedure. Therefore, no clinical studies could be categorized according to the IDEAL Framework. For WEB devices, 6229 articles were screened of which 21 were included. In contrast to EEMS, two studies were categorized as 2a and two as 2b. CONCLUSION: The results of this systematic review demonstrate that both EEMS and WEB devices were not introduced according to the (later developed in the case of EEMS) IDEAL framework. Elements of the framework such as informed consent, ethical approval, and rigorous outcomes reporting are important and could serve to improve the quality of neurosurgical research. Alternative study designs and the use of big data could be useful modifications of the IDEAL framework for innovation in neurosurgery.

Ischemic stroke after radiation therapy for pituitary adenomas: a systematic review.

Radiation therapy is widely used for the treatment of residual and recurrent pituitary adenomas and proved to effectively control tumor growth. However, it is suggested that this treatment might result in an increased risk of ischemic stroke. This review aims to evaluate the radiotherapy-related risk of stroke in pituitary adenoma patients. PubMed and Embase databases were systematically searched for current literature on ischemic stroke risk after radiotherapy in pituitary adenoma, in accordance with the PRISMA statement. Two authors independently selected eligible studies and extracted data. The New Castle Ottawa-scale was used for quality assessment. Out of 264 publications, 11 studies were selected, including 4394 irradiated patients. Incidence of ischemic stroke ranged from 0 to 11.6% (mean 6.7%). While one large, long term follow-up study showed a threefold increased risk of stroke after radiation therapy, another nationwide study of high quality found no significant difference in stroke risk after irradiation. Four studies, which applied stereotactic radiosurgery (SRS) or Gamma-knife surgery (GKS), found no ischemic strokes. Included studies described different radiation techniques and regimens and different lengths of follow-up. In conclusion, complications of cerebral ischemia after radiotherapy for pituitary adenoma are infrequently reported. Moreover, after correction for several confounders, no significant difference in ischemic stroke rate between irradiated and non-irradiated patients could be identified.